Open Access

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

  • Muammer Karadeniz6Email author,
  • Mehmet Erdoğan1,
  • Zengi Ayhan1,
  • Murat Yalcın5,
  • Murat Olukman4,
  • Sevki Cetinkalp1,
  • Gulinnaz E Alper2,
  • Zuhal Eroglu3,
  • Asli Tetik3,
  • Vildan Cetintas3,
  • Ahmet G Ozgen1,
  • Fusun Saygılı1 and
  • Candeger Yılmaz1
Lipids in Health and Disease201110:193

DOI: 10.1186/1476-511X-10-193

Received: 18 August 2011

Accepted: 28 October 2011

Published: 28 October 2011

Abstract

Background

Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.

In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.

Results

In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

Conclusions

We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

Introduction

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases and typically presents with chronic anovulation and hyperandrogenism [1]. PCOS is a common endocrine disorder, affecting between 4% and 8% of the women of reproductive age [2]. PCOS usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS have an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility [3]. Studies suggest that PCOS is associated with increased risk of coronary heart disease (CHD) [4]. Elevated plasma Hcy levels and oxidative stress parameters are considered as an independent risk factor for CVD [57].

Dyslipidemia is possibly the most common metabolic abnormality of PCOS, although the findings of relevant studies have been variable and a substantial percentage of women with PCOS might still have normal lipid profiles [8]. Qualitative alterations of lipoproteins have also been described in PCOS [9].

Obesity, IR and hyperandrogenism, crucial parameters of PCOS play significant pathophysiological roles in lipidemic aberrations associated with the syndrome. IR represents another key factor implicated in the dyslipidemia of PCOS. Glueck et al. reported that 46% of women with PCOS suffered from the metabolic syndrome. Within this subgroup of women, lipid abnormalities were found to be extremely common. 95% of these women demonstrated decreased levels of high-density-lipoprotein (HDL), whereas 56% had hypertriglyceridemia [10].

Lean women with PCOS were shown to have decreased HDL and HDL2 levels when compared to women with normal ovarian function, whereas obese PCOS women also had elevated triglyceride levels [11].

Hyperlipidemia was frequently connected with the disorders in apolipoproteins, receptors, enzymes, or cofactors in proteins related to lipoprotein metabolism. The changes happened in ABCA1 gene can play an important role amongst these changes. ABCA1 gene was considered to be responsible for the cause of Tangier disease [12].

Luciani and collagues were defined ABC transporter family for the first time in 1994. ATP-binding cassette (ABC) genes encode a large family of transmembrane proteins. These proteins bind ATP in order to control the transition of different molecules (such as cholesterol) from cell membranes [13].

This study aims at exploring the association between metabolic, oxidative stress parameters (including malondialdehyde, (MDA) nitric oxide (NO) and disulfide levels (SH)) and demographic parameters and ABCA1 gene polymorphisms in polycystic ovary syndrome patients.

Materials and methods

Patients

In this study, we studied 98 PCOS patients and 93 healthy controls. All researchs with human samples were done with written informed consent of the patients and with approval of the ethical committee of the Ege Universty Hospital. The patients had been referred to the Endocrinology and Metabolism Disease outpatient clinic at the Ege University Hospital. PCOS was defined by the Rotterdam PCOS consensus criteria [14]. Patients who had DM, hyperprolactinemia, congenital adrenal hyperplasia (diagnosed with the adrenocorticotropic hormone stimulation test), thyroid disorders, Cushing's syndrome, hypertension, hepatic or renal dysfunction were excluded from the study. Confounding medications, including oral contraceptive agents, hypertensive medications and insulin-sensitizing drugs, and those which may affect the metabolic criteria were questioned. Another 93 healthy young volunteer females matched for age, body mass index (BMI), and allele frequency were included from the study, and considered as the control group. Their health state was determined by medical history, physical and pelvic examination, and complete blood chemistry. The patients with PCOS and the control group were genetically unrelated.

Study protocol

At study entry, all subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin and ABCA genetic study. All blood samples were obtained in the morning between 08.00 and 09.00 hours after an overnight fasting, and resting in bed during early follicular phase of the spontaneous or P-induced menstrual cycle. During the same visit, all subjects underwent anthropometric measurements including BMI and detail history, systolic and diastolic blood pressure. In present study, data related to the serum malondialdehyde, nitric oxide and disulfide levels, homocystein and fibrinogen levels and the genetic evaluation of ABCA will be shown and discussed.

Biochemical assay

Serum total cholesterol, LDL and HDL cholesterol were measured by Olympus AU 2700 automated analyzer. Plasma insulin concentrations were determined by Immunolite 2000 using two-site chemiluminescent immunometric assay.

Methods for plasma MDA, NO, total sulfhydryl group measurements

All reagents were purchased from Sigma and Merck. MDA was determined by a modified spectrophometric method of Yagi K [15] using tetrametoxypropan as Standard and BioTek MicroQuant microplate reader. NO was determined by measuring stable NO end-products-nitrite and nitrate levels using Miranda's spectrophometric method [16], while total sulfhydryl groups was measured using Ellman's reagent by Sedlak and Lindsay's method [17].

Measurement of plasma homocysteine

Venous blood samples were centrifuged at 1000× g for 10 min and the serums were stored at -80°C until the analysis -not exceeding three months. In this study, serum total homocysteine levels were measured by Fluorescence Polarization Immunoassay Method (IMX Homocysteine Assay, Abbott Diagnostics No: 7D29-20). Dilution method was used for those whose serum homocysteine levels were higher than 50 μmol/L. All samples were prepared as 200 μl. Three controls were used in each sample for calibration of the device. For each of the controls, the results including ranges were accepted as low control (5, 25-8, 75), medium control (10.0-15.0), and high control (20.0-30.0) μmol/ml.

Genetic Analysis

DNA isolations were carried out by using High Pure PCR Template Preparation Kit (Roche Applied Science, Germany) from peripheral blood samples of control and study group cases taken to tubes with EDTA.

For ABCA 1 G1051A polymorphism analysis, by using Forward Primer: 5'-CTC CAA AAGACT TCA AGG ACC C-3', Reverse Primer: 5'-GGC CCA AAA GTC TGA AAG AAC AC-3' primer pair, a DNA fragment of 433 base pairs is amplified by PCR method. For each sample, 25 μl of prepared PCR reaction mixture contains 16, 75 μl of sterile distilled water, 0,5 μl of Forward primer (100 p μl), 0,5 μl of Reverse primer (100 p μl), 2,5 μl Mg+2 (25 mM), 2 μl of dNTP mixture (2 mM), 0,25 μl of Taq DNA polymerase (5 U/μl), and 2,5 μl of genomic DNA.

i - PCR amplification

Denaturation is carried out at 95°C for 2 minutes, amplification at 94°C for 30 seconds as 35 cycles, 1 minute at 72°C, prolongation at 72°C for 7 minutes by applying PCR protocol.

For ABCA1 G2706A polymorphism analysis, DNA fragment of 350 base pairs is amplified by using Forward Primer: 5'-CAA GTG AGT GCT TGG GAT TG-3', Reverse Primer: 5'-TGC TTT TAT TCA GGG ACT CCA-3' primer pairs by PCR method. For each sample, 25 μl of PCR reaction mixture contains 17, 25 μl of sterile distilled water, 0,5 μl of Forward primer (100 p μl), 0,5 μl of Reverse primer (100 p μl), 2,5 μl Mg+2 (25 mM), 1,5 μl of dNTP mixture (2 mM), 0,25 μl of Taq DNA polymerase (5 U/μl), and 2,5 μl of genomic DNA.

ii - PCR amplification

Denaturation is carried out for ten minutes at 94°, amplification for 30 seconds at 94°C as 40 cycles, for 45 seconds at 52°C, 1 minutes at 72°C, prolongation for 7 minutes at 72°C by applying PCR protocol. The size of the products obtained after PCR is controlled at gel electrophoresis. PCR products made for the analysis of ABCA 1 G1051A and G2706A gene polymorphisms are evaluated in agarose gel of 2%.

G1051A polymorphism analysis of -ABCA 1 gene is carried out at 37°C for 6 hours by incubating RFLP reaction mixture of 30 μl containing 17 μl of distilled water, 10 μl of PCR product, 2 μl of Buffer O, and 1 μl of EcoO109I enzyme.

G2706A polymorphism analysis of -ABCA 1 gene is carried out by incubating at 30°C for 3 hours the mixture of RFLP reaction of 30 μl containing 17 μl of distilled water, 10 μl of PCR product, 2 μl of Buffer O, and 1 μl of BsaAI enzyme.

Genotyping is carried out after having conducted and displayed the products obtained as a result of enzyme cut for G1051A polymorphism analysis of ABCA 1 gene in agarose gel of 2% and in agarose gel of 3% for G2706A polymorphism analysis.

As a result of G1051A polymorphism analysis, DNA fragments of sizes of 189 base pairs, 131 base pairs, and 113 base pairs in cases of wild genotype, 320 base pairs, 189 base pairs, 131 and 113 base pairs in heterozygote cases, and 320 base pairs and 113 base pairs in mutant cases are obtained (Figure 1). As a result of G2706A polymorphism analysis, DNA fragments of sizes of 252 base pairs and 98 base pairs in cases of wild genotype, 350 base pairs, 252 base pairs and 98 base pairs in heterozygote cases, and 350 base pairs in mutant cases are obtained (Figure 2).
https://static-content.springer.com/image/art%3A10.1186%2F1476-511X-10-193/MediaObjects/12944_2011_Article_581_Fig1_HTML.jpg
Figure 1

RFLP patterns of ABCA1 G1051A gene obtained with StyI restriction endonuclease. Lane1. 50 bp DNA ladder (Fermentas); Lane2. GG genotype; Lane3. AA genotype; Lanes 4,5,6,7,8,9. GA genotypes.

https://static-content.springer.com/image/art%3A10.1186%2F1476-511X-10-193/MediaObjects/12944_2011_Article_581_Fig2_HTML.jpg
Figure 2

RFLP patterns of ABCA1 G2706A gene obtained with BasaI restriction endonuclease. Lane1. 50 bp DNA ladder (Fermentas); Lanes 2, 4,5,6,8 GA genotypes; Lanes 3, 7 GG genotypes.

Results

I-Demographic, metabolic and oxidative stress parameters of patients and controls

The demographic, hormonal and metabolic parameters of the PCOS and control groups are shown in Table 1. In the PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly (P < 0.05) different in comparison with healthy women (Table 1). The fasting glucose levels were significantly (P < 0.05) higher in PCOS than in control women, whereas no difference was observed in fasting insulin concentrations between the groups (Table 1). No significant differences were detected in age, weight, BMI, homocystein, MDA, NO, SH, estradiol, DHEAS, prolactin, HDL-cholesterol levels between two groups (Table 1).
Table 1

Clinical characteristics of patients and controls

 

Control Group

PCOS Group

p

 

Mean ± SD

Mean ± SD

 

Age (years)

25,63

7,67

24,44

5,69

0,567

Weight

60,43

15,37

66,17

16,08

0,099

BMI (k/m 2 )

24,25

7,68

24,80

5,88

0,436

HCY μmol/ml.

10,90

3,60

12,37

4,05

0,073

MDA (nMol/ml)

6,47

3,63

5,59

2,55

0,396

NO (microMol/L)

8,73

3,04

9,54

4,16

0,595

SH (mMol/L)

6,96

6,07

10,92

7,76

0,172

TAFI

9,89

5,06

12,14

10,01

0,563

Fasting Glucose (mg/dl)

84,39

18,27

91,79

8,99

0,005

Fasting insulin (mIU/ml)

11,09

21,22

15,78

33,23

0,507

Homocysteine (μmol/L)

1,27

1,24

3,83

9,17

0,168

Estradiol (pg/ml)

51,65

58,40

35,13

26,82

0,052

DHEA-S (μg/dl)

272,93

131,36

217,19

115,69

0,035

17 -OHP (ng/ml)

1,10

1,05

1,85

1,04

0,002

Total-Testosterone (ng/ml)

0,92

1,30

0,96

1,85

0,905

Free-Testosterone (pg/ml)

1,76

0,83

3,28

2,12

0,001

Prolactin (pmol)

17,09

10,76

17,01

8,00

0,969

Total-cholesterol (mg/dl)

171,34

61,74

198,95

41,19

0,009

Triglycerides (mg/dl)

88,52

50,83

124,00

69,35

0,014

HDL-C (mg/dl)

59,37

16,39

57,06

15,39

0,514

LDL-C (mg/dl)

98,89

31,83

117,68

31,71

0,01

Fibrinogen (mg/dl)

295,85

102,07

373,83

110,84

0,004

II-Allelic distributions and ABCA genotype frequencies in patients

The frequency of ABCA G1051A and G2706A polymorphism are shown in Table 2. The allelic distribution of ABCA genotypes was in Hardy-Weinberg equilibrium for both groups of women.
Table 2

Distribution of ABCA haplotypes and genotypes

Polymorphism

Genotypes/Haplotypes

Control

Group

n = 93

PCOS

Group

n = 98

OR*

95% CI*

P*

G1051A

GG (Wild type)

34

36,6%

30

31,2%

R

0.585

 

GA (Heterozygote)

49

52,7%

53

53,8%

0,836

0,444-1,574

0,579

 

AA (Mutant)

10

10,8%

15

15,1%

0,609

0,235-1,577

0,307

 

G

117

62,9%

114

58,1%

0.817

0.538-1.238

0.396

 

A

69

37,1%

82

41,9%

   

G2706A

GG (Wild type)

55

60,7%

80

82,6%

R

0.004

 

GA (Heterozygote)

30

32,1%

9

8,7%

5,029

1,922-13,160

0.001

 

AA (Mutant)

8

7,1%

9

8,7%

1,118

0,339-3,685

0.855

 

G

162

87,0%

150

76,8%

2.016

1.094-3.714

0.027

 

A

24

13,0%

46

23,2%

   

The genotype ABCA G1051A distribution didn't differ between the control group (GG 31.2%, AG 53.8%, AA 15.1%) and the PCOS patients (GG 36.6%, AG 52.7%, AA 10.8%) (P > 0.05) The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%) (P < 0.05). The frequency of the polymorphic A allele (ABCA G2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively (p = 0.027, OR:2.016; Table 2).

III-Effects of ABCA genotypes on lipid profile, demographic and other metabolic parameters in patients

There was no statistically significant difference in PCOS patients between ABCA G1051A genotypes (AA, GA and GG) and BMI, fasting insulin, fasting glucose, triglyceride levels, HDL levels, LDL levels, fasting blood glucose levels, f-testosterone, fibrinogen and 17-OHP levels (p > 0.05; Table 3). The fasting insulin level was significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes (Table 3). No statistically meaningful difference was determined between polymorphism and lipid and other parameter levels in patients carrying ABCA1 G2706A polymorphism (Table 4).
Table 3

Biochemical and Hormonal parameters between ABCA G1051A genotypes in patient group

 

G1051A Genotype

Mean

SD

95% CI

p

BMI (k/m2)

GG

23,64

5,11

21,62-25,66

0,353

 

GA

25,45

6,386

23,46-27,44

 
 

AA

26,3

6,277

21,81-30,79

 

Fasting Glucose (mg/dl)

GG

91,63

6,264

89,15-94,11

0,291

 

GA

91,79

7,537

89,44-94,13

 
 

AA

96,09

14,883

86,09-106,09

 

Fasting insulin (mIU/ml)

GG

10,2394

4,98809

8,44-12,04

0,001

 

GA

10,7138

4,53637

9,45-11,97

 
 

AA

21,5954

5,05475

8,87-34,32

 

Homocysteine (μmol/L)

GG

2,3526

1,21

1,91-2,79

0,003

 

GA

2,3925

1,18

2,06-2,72

 
 

AA

4.11

3,27

2,04-6,19

 

Estradiol (pg/ml)

GG

29,57

17,069

22,36-36,78

0,226

 

GA

40,74

33,594

29,69-51,78

 
 

AA

29,33

12,952

19,38-39,29

 

DHEA-S (μg/dl)

GG

205,46

90,094

169,07-241,85

0,645

 

GA

229,45

126,715

188,92-269,98

 
 

AA

202,78

112,325

116,44-289,12

 

17 -OHP (ng/ml)

GG

1,878

0,846

1,543-2,212

0,906

 

GA

1,835

1,2192

1,445-2,225

 
 

AA

1,709

0,8723

1,123-2,295

 

Free-Testosterone (pg/ml)

GG

3,16

2,009

2,35-3,97

0,63

 

GA

3,11

2,248

2,4-3,82

 
 

AA

3,8

1,982

2,47-5,13

 

Total-Testosterone (ng/ml)

GG

1,278

3,0116

0,024-2,581

0,582

 

GA

0,748

0,8182

0,458-1,039

 
 

AA

0,813

0,2997

0,562-1,063

 

Prolactin (pmol)

GG

17,61

9,731

13,76-21,46

0,568

 

GA

16,07

7,293

13,67-18,46

 
 

AA

18,8

6,125

14,42-23,18

 
Table 4

Biochemical and Hormonal parameters between G2706A genotypes in PCOS patient group

 

G2706A Genotype

Mean

SD

95% CI

p

BMI (k/m2)

GG

24,47

5,17

23,01-25,92

0,071

 

GA

28,42

7,01

21,06-35,77

 
 

AA

20,63

1,25

18,64-22,61

 

Fasting Serum Glucose (mg/dl)

GG

92,82

10,28

89,93-95,71

0,691

 

GA

89,83

6,94

82,55-97,12

 
 

AA

90,00

4,32

83,13-96,87

 

Fasting insulin (mIU/ml)

GG

12,5701

10,69

10,04-15,10

0.560

 

GA

9,6271

4,12

7,25-12,00

 
 

AA

11,5217

4,24

8,82-14,22

 

Homocysteine (μmol/L)

GG

2,7138

1,84

2,27-3,15

0.491

 

GA

2,1653

0,97

1,60-2,73

 
 

AA

2,3987

1,21

1,63-3,17

 

Estradiol (pg/ml)

GG

34,72

28,55

26,43-43,01

0,499

 

GA

45,75

30,71

3,11-94,61

 
 

AA

50,50

47,90

25,72-126,72

 

DHEA-S (μg/dl)

GG

216,10

101,88

186,52-245,69

0,079

 

GA

302,67

156,34

138,60-466,74

 
 

AA

148,75

100,73

11,54-309,04

 

17 -OHP (ng/ml)

GG

1,992

1,14

1,664-2,320

0,823

 

GA

1,767

1,13

0,584-2,950

 
 

AA

1,725

0,60

0,767-2,683

 

Prolactin (pmol)

GG

17,20

8,87

14,62-19,77

0,758

 

GA

15,50

4,28

11,01-19,99

 
 

AA

14,50

3,51

8,91-20,09

 

Free-Testosterone (pg/ml)

GG

3,49

2,48

2,77-4,20

0,839

 

GA

3,92

1,48

2,36-5,47

 
 

AA

3,03

1,19

1,13-4,92

 

Total-Testosterone (ng/ml)

GG

1,041

2,32

0,288-1,794

0,671

 

GA

1,900

1,96

1,224-5,024

 
 

AA

,525

0,30

0,050-1,000

 

IV-Effects of ABCA genotypes on oxidative stress markers, homocystein levels in patients

In our study, the homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes (Table 3). The ABCA genotypes do not appear to have significant correlation with the plasma Hcy levels, MDA, NO and SH in PCOS patients.

Discussion

Women with PCOS have multiple risk factors for the development of cardiovascular disease, including hyperandrogenemia, insulin resistance and glucose intolerance, obesity, and central fat deposition [18]. Women with PCOS are also at increased risk for the development of the metabolic syndrome [19, 20].

Additionally, different markers of clinical and subclinical atherosclerosis, including serum markers (for example fibrinogen, high sensitive C-reactive protein and homocysteine, oxidative stress markers, PAI-1, TPA), carotid intimae-media thickness, and echocardiographic findings have also been found to be changed [2125]. In our study, no meaningful correlation between homocystein, NO MDA, and SH levels between patient and control groups. Fibrinogen levels were found to be statistically higher in PCOS patients group than the controls. However, homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

Women with PCOS have a higher prevalence and a greater degree of hyperinsulinemia, and insulin resistance than weight-matched control subjects [2628]. However, in our study, fasting insulin levels were not different from the controls when compared to healthy controls.

Dyslipidemia is a common metabolic abnormality in PCOS, although the reported types and extent of lipid aberrations have been variable [29, 30]. PCOS women have been demonstrated to have substantially higher TC and LDL levels than control women < 45-years-old, after adjustment for BMI and hyperinsulinemia [31].

IR represents another key factor implicated in the dyslipidemia of PCOS. Glueck et al. reported that 46% of women with PCOS suffered from the metabolic syndrome [32]. Within this subgroup of women, lipid abnormalities were found to be extremely common. 95% of these women demonstrated decreased levels of high-density-lipoprotein (HDL), whereas 56% had hypertriglyceridemia. In this study, no difference was determined in PCOS patient group in terms of HDL cholesterol when compared to the controls, while TG values were determined to be statistically meaningfully high in patient group. In this study, LDL cholesterol and total cholesterol levels were found to be statistically meaningfully high in PCOS patient group when compared to the controls.

IR and compensatory hyperinsulinemia are considered to be main responsible for the lipidemic aberrations of obesity and PCOS. Besides, genetic factors may also contribute to the formation of dyslipidemia in PCOS disease [33]. Members of the ATP-binding cassette (ABC) transporter family, such as ABCA1, have been shown to control cellular lipid metabolism [34, 35]. Changes happened in ATP binding cassette transporter 1 (ABC1) gene encoding a protein regulating entry and exit from cell membrane may contribute to dyslipidemia in patients with PCOS.

Jerome I. Rotter et al. found a relation between ABCA1 G1051A polymorphism and HDL-cholesterol elevation. This relation conflicts with previous studies. Again, these researchers determined a correlation between ABCA1 G1051A gene polymorphism and moderate LDL-cholesterol lowness [36, 37]. In our study, the genotype ABCA G1051A distribution didn't differ between control and PCOS groups. However, the distribution of ABCA G2706A genotype differed between the control group and the PCOS patients. Frikke-Schmidt et al. determined higher G2706A gene polymorphism allele in patient group with low HDL cholesterol [38]. In our study, the frequency of the polymorphic A allele of ABCA G2706A gene was higher in PCOS patients than control group.

There was no statistically significant difference in PCOS patients between ABCA G1051A genotypes (AA, GA and GG) and BMI, fasting insulin, fasting glucose, triglyceride levels, HDL levels, LDL levels, fasting blood glucose levels, f-testosterone, fibrinogen and 17-OHP levels. However, in PCOS patients, fasting insulin levels and homocystein were found to be significantly higher in ABCA G1051A mutant genotype than heterozygote and wild genotypes.

In conclusion, we found AA genotype and A allele of ABCA G2706A in PCOS patients. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. However, it is determined that ABCA1 G2706A and ABCA G1051A polymorphisms have no effect on lipid oxidative stress parameters in patients. Future studies should explain the specific roles of other genes (e.g CETP, LDL receptor and hepatic lipase) in the pathophysiology of dyslipidemias in PCOS.

Declarations

Authors’ Affiliations

(1)
Department of Endocrinology, Ege University School of Medicine
(2)
Department of Biochemistry, Ege University School of Medicine
(3)
Department of Medical Biology, Ege University School of Medicine
(4)
Department of Pharmacology, Ege University Hospital, Ege University School of Medicine
(5)
Division of Internal Medicine, Sifa University, Health Application and Research Center
(6)
Department of Endocrinology, Sifa University, Health Application and Research Center

References

  1. Chang RJ: A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004, 191: 713-7. 10.1016/j.ajog.2004.04.045View ArticlePubMedGoogle Scholar
  2. King J: Polycystic ovary syndrome. J Midwifery Womens Health. 2006, 51: 415-22. 10.1016/j.jmwh.2006.01.008View ArticlePubMedGoogle Scholar
  3. Otto-Buczkowska E, Jarosz-Chobot P, Deja G: [Early metabolic abnormalities--insulin resistance, hyperinsulinemia, impaired glucose tolerance and diabetes, in adolescent girls with polycystic ovarian syndrome]. Przegl Lek. 2006, 63: 234-8.PubMedGoogle Scholar
  4. Barutcuoglu B, Bozdemir AE, Dereli D, Parildar Z, Mutaf MI, Ozmen D, Bayindir O: Increased serum neopterin levels in women with polycystic ovary syndrome. Ann Clin Lab Sci. 2006, 36: 267-72.PubMedGoogle Scholar
  5. Refsum H, Ueland PM, Nygard O, Vollset SE: Homocysteine and cardiovascular disease. Annu Rev Med. 1998, 49: 31-62. 10.1146/annurev.med.49.1.31View ArticlePubMedGoogle Scholar
  6. Gadducci A, Gargini A, Palla E, Fanucchi A, Genazzani AR: Polycystic ovary syndrome and gynecological cancers: is there a link?. Gynecol Endocrinol. 2005, 20: 200-8. 10.1080/09513590400021201View ArticlePubMedGoogle Scholar
  7. Balen A: Polycystic ovary syndrome and cancer. Hum Reprod Update. 2001, 7: 522-5. 10.1093/humupd/7.6.522View ArticlePubMedGoogle Scholar
  8. Legro RS, Kunselman AR, Dunaif A: Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med. 2001, 111: 607-613. 10.1016/S0002-9343(01)00948-2View ArticlePubMedGoogle Scholar
  9. Berneis K, Rizzo M, Lazzarini V, Fruzzetti F, Carmina E: Atherogenic lipoprotein phenotype and low density lipoproteins size and subclasses in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007, 92: 186-189.View ArticlePubMedGoogle Scholar
  10. Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L: Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism. 2003, 52: 908-915. 10.1016/S0026-0495(03)00104-5View ArticlePubMedGoogle Scholar
  11. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS: Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf). 1992, 37: 119-125. 10.1111/j.1365-2265.1992.tb02295.x.View ArticleGoogle Scholar
  12. Oram JF: Tangier disease and ABCA1. Biochim Biophys Acta. 2000, 1529: 321-30.View ArticlePubMedGoogle Scholar
  13. Luciani MF, Chimini G: The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death. EMBO J. 1996, 15: 226-35.PubMed CentralPubMedGoogle Scholar
  14. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19: 41-7.View ArticleGoogle Scholar
  15. Yagi K: Lipid peroxides in hepatic, gastrointestinal and pancreatic diseases. Free radicals in Diagnostic Medicine. Edited by: Armstrong D. 1994, 165-169. New York, NY, Plenum Press,View ArticleGoogle Scholar
  16. Miranda KM, Espey MG, Wink DA: A rapid, simple spectrophometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001, 5: 62-71. 10.1006/niox.2000.0319View ArticlePubMedGoogle Scholar
  17. Sedlak J, Lindsay RH: Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968, 25: 192-205.View ArticlePubMedGoogle Scholar
  18. Tsilchorozidou T, Overton C, Conway GS: The pathophysiology of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004, 60: 1-17. 10.1046/j.1365-2265.2003.01842.x.View ArticleGoogle Scholar
  19. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE: Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005, 90: 1929-1935. 10.1210/jc.2004-1045View ArticlePubMedGoogle Scholar
  20. Wild R: Polycystic ovary syndrome: A risk for coronary artery disease?. Am J Obstet Gynecol. 2002, 186: 35-43. 10.1067/mob.2002.119180View ArticlePubMedGoogle Scholar
  21. Tarkun I, Arslan BC, Cantürk Z, Türemen E, Sahin T, Duman C: Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab. 2004, 89: 5592-6. 10.1210/jc.2004-0751View ArticlePubMedGoogle Scholar
  22. Tarkun I, Cetinarslan B, Türemen E, Sahin T, Cantürk Z, Komsuoglu B: Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome. Eur J Endocrinol. 2005, 153: 115-21. 10.1530/eje.1.01948View ArticlePubMedGoogle Scholar
  23. Karadeniz M, Erdogan M, Berdeli A, Tamsel S, Saygili F, Yilmaz C: The progesterone receptor PROGINS polymorphism is not related to oxidative stress factors in women with polycystic ovary syndrome. Cardiovasc Diabetol. 2007, 5: 6-29.Google Scholar
  24. Karadeniz M, Erdogan M, Berdeli A, Saygili F, Yilmaz C: 4 G/5 G polymorphism of PAI-1 gene and Alu-repeat I/D polymorphism of TPA gene in Turkish patients with polycystic ovary syndrome. J Assist Reprod Genet. 2007, 24: 412-8. 10.1007/s10815-007-9160-7PubMed CentralView ArticlePubMedGoogle Scholar
  25. Karadeniz M, Erdoğan M, Tamsel S, Zengi A, Alper GE, Cağlayan O, Saygili F, Yilmaz C: Oxidative stress markers in young patients with polycystic ovary syndrome, the relationship between insulin resistances. Exp Clin Endocrinol Diabetes. 2008, 116: 231-5. 10.1055/s-2007-992154View ArticlePubMedGoogle Scholar
  26. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A: Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987, 65: 499-507. 10.1210/jcem-65-3-499View ArticlePubMedGoogle Scholar
  27. Conway GS, Jacobs HS, Holly JM, Wass JA: Effects of luteinizing hormone, insulin, insulin-like growth factor-I and insulin-like growth factor small binding protein 1 in the polycystic ovary syndrome. Clin Endocrinol (Oxf). 1990, 33: 593-603.View ArticleGoogle Scholar
  28. Dunaif A, Segal KR, Futterweit W, Dobrjansky A: Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989, 38: 1165-1174. 10.2337/diabetes.38.9.1165View ArticlePubMedGoogle Scholar
  29. Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB: Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1985, 61: 946-951. 10.1210/jcem-61-5-946View ArticlePubMedGoogle Scholar
  30. Rajkhowa M, Neary RH, Kumpatla P, Game FL, Jones PW, Obhrai MS, Clayton RN: Altered composition of high density lipoproteins in women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1997, 82: 3389-3394. 10.1210/jc.82.10.3389PubMedGoogle Scholar
  31. Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg RA: Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol. 1998, 51: 415-422. 10.1016/S0895-4356(98)00010-9View ArticlePubMedGoogle Scholar
  32. Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L: Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism. 2003, 52: 908-915. 10.1016/S0026-0495(03)00104-5View ArticlePubMedGoogle Scholar
  33. Cetinkalp S, Karadeniz M, Erdogan M, Zengi A, Cetintas V, Tetik A, Eroglu Z, Kosova B, Ozgen AG, Saygili F, Yilmaz C: Apolipoprotein E gene polymorphism and polycystic ovary syndrome patients in Western Anatolia, Turkey. J Assist Reprod Genet. 2009, 26: 1-6. 10.1007/s10815-008-9280-8PubMed CentralView ArticlePubMedGoogle Scholar
  34. Oram JF, Lawn RM: ABCA1: the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res. 2001, 42: 1173-1179.PubMedGoogle Scholar
  35. Wang N, Silver DL, Thiele C, Tall AR: ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein. J Biol Chem. 2001, 276: 23742-23747. 10.1074/jbc.M102348200View ArticlePubMedGoogle Scholar
  36. Benton JL, Ding J, Tsai MY, Shea S, Rotter JI, Burke GL, Post W: Associations between two common polymorphisms in the ABCA1 gene and subclinical atherosclerosis: Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2007, 193: 352-60. 10.1016/j.atherosclerosis.2006.06.024View ArticlePubMedGoogle Scholar
  37. Cenarro A, Artieda M, Castillo S, Mozas P, Reyes G, Tejedor D, Alonso R, Mata P, Pocoví M, Civeira F, : A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia. J Med Genet. 2003, 40: 163-168. 10.1136/jmg.40.3.163PubMed CentralView ArticlePubMedGoogle Scholar
  38. Frikke-Schmidt , Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A: Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J Clin Invest. 2004, 114: 1343-1353.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Karadeniz et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.