In the current study, we showed that the levels of ApoB were higher whereas the ratio of ApoAI to ApoB was lower in Mulao than in Han (P < 0.05 for each). There were no significant differences in the levels of TC, TG, HDL-C, LDL-C and ApoAI between the two ethnic groups (P > 0.05 for all). In contrast with developed countries, China has experienced a considerable increase in the prevalence of CAD over the past several decades . Evidence of the relationship between dyslipidemia and CAD has been established worldwide. It is well recognized that dyslipidemia is a multifactorial and complicated origin which combined by genetic factors with environmental factors including demographics, diet, alcohol consumption, cigarette smoking, obesity, exercise, hypertension . Thus, prediction of the risk for dyslipidemia on the basis of genetic variants would be beneficial for the personalized prevention of CAD. Recent GWASs and meta-analysis on European population have identified many genes previously implicated in lipid regulation. However, validation of these loci on different global populations is still unclear.
Mulao nationality is one of the 11 minorities in Guangxi Zhuang Autonomous Region, which is a genetic feature distinctive nationality. Strict intra-ethnic marriages have been performed in this population and they have unique lifestyle as well as diet from time immemorial. Therefore, we surmised that the hereditary characteristic and some lipid-related gene polymorphisms in the Mulao population may be different from those in Han nationality.
The genotypic and allelic frequencies of ST3GAL4 rs11220462 SNP in diverse racial/ethnic groups have not been reported. The data in the International HapMap Project’s data-base have showed that the frequencies of A allele and AA, AG genotypes were 42.0%, 15.9% and 52.3% in Han Chinese in Beijing; 30.7%, 9.1% and 43.2% in Japanese; and 15.8%, 1.7% and 0% in Yoruba; respectively. In the present study, we showed that the frequencies of A allele and AA, AG genotypes were 35.5%, 11.2% and 48.7% in Mulao; and 38.3%, 13.0% and 50.6% in Han; respectively. There were no conspicuous differences in the genotypic and allelic frequencies of the rs11220462 SNP between the Mulao and Han populations, or between males and females in the both ethnic groups. As compared with the data in the International HapMap Project’s data-base, we found that the frequencies of the A allele and AA, AG genotypes in our study populations were lower than those in Han Chinese from Beijing, which may be caused by different sample sizes and regions.
The potential association between the rs11220462 SNP and serum lipid levels in humans has been detected in a previous GWAS. Teslovich et al.  showed that the rs11220462 SNP was significant associated with LDL-C concentration (P = 1.20 × 10−15) in population of European descent. In our present study, we found that the levels of TC and LDL-C were different among the AA, AG and GG genotypes of the rs11220462 SNP in Mulao, the A allele carriers had higher serum TC, LDL-C and ApoB levels than the A allele non-carriers in the both males and females. For Han nationality, the levels of TC and TG were also different among the three genotypes in males but not in females, the subjects with AA genotype had higher TC and TG levels than the subjects with AG or GG genotype. These findings suggest that the association of rs11220462 SNP and serum lipid levels is different between the two ethnic groups, and there may be a sex-specific association of rs11220462 SNP and serum lipid parameters in the Han population. These differences may also be related to the variations in examined populations, including physical condition, environmental factors such as diet or under medication. Therefore, the association of the ST3GAL4 rs11220462 SNP and serum lipid levels needs to be further studied with larger sample size.
There was no previous study to report the direct effect of ST3GAL4 rs11220462 SNP on serum lipid levels. We suspected that there may be several potential mechanisms to explain the association between the rs11220462 SNP and serum lipid levels. Firstly, ST3GAL4 encodes a member of the glycosyltransferase 29 family which was associated with increasing risk of type 2 diabetes and cardiovascular disease . Secondly, Adamska et al. reported that the ST3GAL4 plays a key role in the synthesis of E-selectin ligands which is associated with metabolic syndrome and coronary artery calcification. Thirdly, a recent GWAS has identified several intronic SNPs including rs11220462 associated with lipid levels . About 5-10% of genomic variants found in familial hypercholesterolemia are located in the introns of the candidate genes and are classified as splicing mutations . More and more researcher found that intron is involved in mRNA transcription and translation regulation. Finally, microRNAs (miRNAs), a family of small non-coding RNA molecules, appear to regulate animal lipid metabolism and preadipocyte conversion to form lipid-assimilating adipocytes . Recently, genetic model of beef cattle was used to analyze the association between genomic context characteristics of miRNAs (38.7% located in intron) with their function in adipose tissue . The findings suggested that miRNAs play a role in the regulation of bovine adipogenesis and fat metabolism. Taken together, the rs11220462 SNP may act in an intronic variation to influence the ST3GAL4-associated regulatory network or specific miRNAs regulating adipogenesis. However, the biological function and detailed role of ST3GAL4 rs11220462 SNP in lipid metabolism remain unclear and need to be further explored.
It is well realized that environmental factors such as dietary patterns, lifestyle and physical inactivity are all strongly related with serum lipid levels . In the present study, multivariate linear regression analysis also showed that age, sex, BMI, alcohol consumption, cigarette smoking, and blood pressure were involved in determining serum lipid parameters in both ethnic groups. These data suggest that the environmental factors also play an important role in determining serum lipid levels in our study populations. Differences in serum lipid levels between the two ethnic groups could be related to factors such as differences in the genetic background, dietary patterns and lifestyle and their interactions. Although rice and corn are the staple food in the both ethnic groups, the people of Mulao nationality prefer cold foods along with acidic and spicy dishes. Therefore bean soy sauce and pickle vegetables become members of their most popular dishes. Meanwhile, they enjoy eating animal offals which contain abundant saturated fatty acid. For nearly 50 years it has been widely accepted that high-fat diets, particularly those contain rich saturated fatty acids, can raise the serum cholesterol concentrations as well as the risk of suffering cardiovascular disease . Diet alone could be responsible for up to 2.5% of the variability on serum lipid levels [29, 30]. A meta-analysis stated that diet modification is a key strategy for prevention and regression of CAD, and for every 1% decrease in energy consumed as dietary saturated fatty acid, TC decreased by 0.056 mmol/L and LDL-C by 0.05 mmol/L . In addition, we also found that the percentages of smokers were higher in Mulao than in Han nationalities (P <0.05). Over the years, the relationship between cigarette smoking and dyslipidemia has been gotten in focus by more and more investigators. A recent study in smoking males (ages from 25 to 35 years old) has found that a significant increase in TC and LDL-C in tobacco users [32, 33]. Another recent meta-analysis also reported that smoking increased TG by 0.15 mmol/L, and decreased HDL-C by 0.09 mmol/L with every 20 cigarettes smoked . Therefore, the results of exposure to different lifestyle and environmental factors probably further modify the association of genetic variations and serum lipid levels in our study populations.
There are several major strengths in our study. First, the study is an investigation of a representative random sample of the Mulao population, which retains its regional and special customs in China and may be a useful subgroup for population genetic studies. Second, the sample size of the study is moderate with 700 subjects of Mulao and 694 subjects of Han Chinese. Third, a recent GWAS has reported the association between the rs11220462 SNP and serum lipid levels and our present study is the first replication of GWAS signals in the Chinese population to provide significant evidence for the association of the rs11220462 SNP with lipid traits. To interpret the findings, however, several potential limitations in our study should be acknowledged. First, all of the lifestyle, diet pattern and physical activities are the important factors for lipid regulation and prevalence of CAD, however, the cross-sectional study design limits the ability to determine the effects of them during the statistical analysis since they were self-reported and difficult to classify. Second, although we have explored the association of ST3GAL4 rs11220462 SNP and serum lipid levels, there are still many unmeasured environmental and genetic factors such as other ST3GAL4 SNPs and the interactions of gene-gene and/or gene-environment. Finally, the ST3GAL4 rs11220462 SNP is an intronic variation which does not lead to a change in the amino acid sequence of the ST3GAL4. Thus, the effect of the rs11220462 SNP on lipid metabolism may be limited. To confirm our findings, further in-depth studies on the biological actions of ST3GAL4 rs11220462 variation and the interactions of gene-environment are necessary.