Background: Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case-control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed.

Methods: The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR-RFLP assay. Anthropometric measurements were measured in all participants.

Results: There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p=0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA+AA genotypes in male CHD patients (p=0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age<55 (OR=2.837, p=0.001) and TC ≥ 5.18 mmol/L (OR=1.970, p=0.027) in male subjects. However, this association was not observed in female patients (p>0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age<55 years.

Conclusion: These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.