The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease.
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.


CONCLUSIONS
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.
Istanbul University, the Institute of Experimental Medicine, Department of Molecular Medicine, Istanbul, Turkey.
Basak
B
Akadam-Teker
Ozlem
O
Kurnaz
Ender
E
Coskunpinar
Aynur
A
Daglar-Aday
Ozlem
O
Kucukhuseyin
Huseyin Altug
HA
Cakmak
Erhan
E
Teker
Zehra
Z
Bugra
Oguz
O
Ozturk
Hulya
H
Yilmaz-Aydogan
D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D017678:Sex Distribution; D012737:Sex Factors
D008078:Cholesterol, LDL; D002784:Cholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
AD; Alzheimer's disease; BMI; CHD; Coronary heart disease; DBP; HDL-C; HDL-cholesterol; HMGCR; HWE; Hardy–Weinberg equilibrium; Hydroxymethylglutaryl-Coenzyme A Reductase; LDL-C; LDL-cholesterol; Lipoproteins; Polymorphism; SBP; SNP; SREBP; Single Nucleotide Polymorphism; TC; TG; VLDL-C; VLDL-cholesterol; body mass index; coronary heart disease; diastolic blood pressure; sterol regulatory element binding protein; systolic blood pressure; total-cholesterol; triglyceride