Association of CYP7A1 -278A>C polymorphism and the response of plasma triglyceride after dietary intervention in dyslipidemic patients

Abstract

We investigated the effect of the -278A>C polymorphism in the CYP7A1 gene on the response of plasma lipids to a reduced-fat diet for 6 to 8 weeks in a group of 82 dyslipidemic males with a mean age of 46.0 ± 11.7 years. Individuals who presented at least one high alteration in total cholesterol, low-density lipoprotein cholesterol or triglyceride values were considered to be dyslipidemic. Exclusion criteria were secondary dyslipidemia due to diabetes mellitus, renal, liver, or thyroid disease. None of the subjects were using lipid-lowering medication. Baseline and follow-up lipid concentrations were measured. The genotypes were determined by the digestion of PCR products with the BsaI restriction endonuclease. There were statistically significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations after dietary intervention. The minor allele C has a frequency of 43%. Carriers of the C allele had significantly lower triglyceride concentrations (P = 0.02) than AA homozygotes. After adjustment of covariates, subjects with the AC and CC genotypes showed a greater reduction in triglyceride concentrations compared to subjects with the AA genotype. Multiple linear regression analyses showed that the AC and CC CYP7A1 genotypes accounted for 5.2 and 6.2% of triglyceride concentration during follow-up and adjusted percent of change of triglyceride concentration, respectively. The present study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. This gene represents a potential locus for a nutrigenetic directed approach.

Interactions Between Regulatory Variants in CYP7A1 (Cholesterol 7α-Hydroxylase) Promoter and Enhancer Regions Regulate CYP7A1 Expression

“…In genome wide association studies (GWAS), CYP7A1 single nucleotide polymorphisms (SNPs) associate with total cholesterol and LDL levels 2, 3 , gallstone diseases 4 , and blood deoxycholic acid 5 . Candidate gene studies also reveal associations between CYP7A1 and total cholesterol and triglyceride levels 6, 7 , response to statins 8–10 , atherosclerosis 11 , ischemic stroke 12 , hypertension 13 , coronary artery disease (CAD) 14 , colorectal cancer 15 , biliary cirrhosis 16 , gallbladder cancer 17 , diabetes 5 , and anti-tuberculosis drug-induced hepatotoxicity 18 . These associations highlight the biological relevance of cholesterol-bile acid homeostasis, with apparently opposite effects of CYP7A1 activity on CAD and diabetes.…”

Effect of polymorphisms in the CD36 and STAT3 genes on different dietary interventions among patients with coronary artery disease: study protocol for a randomized controlled trial

“…Barcelos et al [33], for instance, showed that the -278A>C (rs3808607) polymorphism in the CYP7A1 gene can modify serum triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population; in other study, the consumption of 1 unit of Brazil nuts a day increased the selenium status and the glutathione peroxidase-1 (GPx1) activity in obese women, regardless of the GPx1 Pro198Leu polymorphism [34]. The Brazilian population is considered one of the most ethnically mixed in the world [35], and this must be considered before all interpretations regarding genetic studies.…”

The Effect of CYP7A1 Polymorphisms on Lipid Responses to Fenofibrate

“…However, in response to a high intake of dietary cholesterol, the minor G allele was associated with a higher response of HDL-C and total cholesterol compared to non-carriers [12]. Likewise, individuals carrying the minor G allele experienced a greater reduction of plasma TG levels than did those non-carriers after a 6- to 8-week low-fat diet in a group of dyslipidemic males [11]. Despite the inconsistent directionality of the allele effect, current studies provide evidence that the m204T>G SNP significantly determines the effect of lipid-lowering drug and thus, may predict the future clinical CVD event.…”

“…The observed conflicting effects on plasma triglycerides could be due to sex, genetic background, diet or other environmental factors, more importantly, may reflect the complex role of CYP7A1 and bile acid biosynthesis in maintaining the homeostasis of the anabolic lipoprotein assembly/secretion pathway with the cholesterol catabolic pathway. The common variants at the CYP7A1 locus, promoter variant m204T>G (rs3808607) in particular, have been studied extensively yielding descriptions of genetic impact on hydroxylase activity, fasting plasma LDL cholesterol and triglyceride [8-10] as well as modulation of lipid responses to statin treatment and dietary manipulations [11, 12]. …”