In this haplotype-based case–control study, we found GGGT haplotype carriers have higher risk but GGTA haplotype carriers have decreased risk for CHD in Han Chinese population. To the best of our knowledge, this is the first study to reveal the relation between CYP4F2 polymorphisms and CHD in Chinese Han population.
The genetic variation is the molecular basis of human genetic diversity. The T allele of CYP4F2 rs2108622 represents a missense mutation that results in the change of valine 433 to methionine (V433M). This change in the primary structure of CYP4F2 affects enzyme activity, leading to changes in drug metabolism, physiology, and pathophysiology. Cha et al.  through a genome-wide association study identified rs2108622 as a genetic determinant of warfarin responsiveness for Japanese. However, no association was found between this SNP and CHD by a genome-wide association study approach. CHD is caused by the interaction between environmental and genetic factors. In this study, an important human metabolic enzyme P450 gene family member- CYP4F2 gene was selected as the candidate gene to perform the case–control study, and we found that rs2108622 and rs3093105 in CYP4F2 gene was significantly associated with higher risk for CHD. We also found GGGT haplotype consisting of rs2108622-rs3093100-rs3093105-rs3093135 was the susceptibility haplotype of CHD. Our results were consistent with the results reported by Fu et al. , but inconsistent with results by Ward et al.  and Fava et al. . Ward et al. found that the A allele was a risk factor for hypertension. The other study by Fava et al.  found that the A allele was a risk factor for IS. This difference may be due to different races, different methodologies and different patient selection criteria.
Singh et al.  found that androgen-induced CYP4A8 expression reduced CYP2C23 expression and caused increased production of 20-HETE, then the epoxyeicosatrienoic acid (EET) decreased to affect the contraction of blood vessels. However, the exact mechanism of the susceptibility for CHD remains unclear.
In addition, although an elevated level of LDL-C and a decreased level of HDL-C in serum are independent risk factors for CHD, we did not find the LDL-C level and HDL-C level to be different between the CHD patients and the control subjects. This phenomenon may be the result from the treatment of decreased-cholesterol drugs (e.g., simvastatin, lovastatin) in CHD patients.
Several limitations of the present study should be noted. Firstly, these findings should be interpreted with caution because the population was only from Chinese population, this fact may reduce the possibility of confounding from ethnicity; Secondly, the present study is a hospital based case–control study, the selection bias cannot be avoidable and the subjects may not be representative of the general population; Finally, in the present study, we did not detect the amount of 20-HETE associated with CYP4F2 polymorphisms.