Associations Between Polymorphisms in the Glucocorticoid-Receptor Gene and Cardiovascular Risk Factors in a Chinese Population

Abstract

BackgroundGlucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population.MethodsWe recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested.ResultsAmong the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004).ConclusionsPolymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease.

BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: the Hoorn and CODAM studies

“…These analyses were adjusted, however, for multiple covariates, including BMI, and could therefore mask the effect of BclI on blood pressure that is possibly partly mediated by BMI. This hypothesis is supported by a Chinese study in a large healthy cohort showing a strong association of BclI with SBP after adjustment only for sex and age (13). To our knowledge, we are the first large observational study reporting higher MAP in homozygous carriers of the BclI polymorphism.…”

“…Some studies found systolic blood pressure (SBP) to be increased for BclI carriers (12,13) and homozygous carriers of the BclI polymorphism (GG) were more common in a group of young adults with higher personal and parental blood pressure (14). Some larger studies, however, did not find this association (10,15,16).…”

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease

“…We found that homozygous carriers of the BclI polymorphism of the GR gene had higher BMI and lower total hydrocortisone equivalent supplementation dose than heterozygous carriers or noncarriers. In earlier studies the BclI polymorphism was found to be associated with increased sensitivity to endogenous glucocorticoids . Our data suggest that the BclI polymorphism may cause increased sensitivity to exogenous glucocorticoids as well, and that the dose of glucocorticoid replacement therapy in patients with Addison's disease may be reduced in homozygous BclI carriers as already proposed .…”

Cardio‐metabolic consequences of glucocorticoid replacement: relevance of ultradian signalling

“…The Tth111I NR3C1 polymorphism appears to play a protective role in the development of coronary artery disease, and homozygous carriers of this allele could be protected against multivessel disease. In a Chinese population, GR gene variants have been associated with cardiovascular risk factors such as BMI, systolic blood pressure and LDL cholesterol levels . The relationship between the GR gene and cardiovascular disease varies substantially among populations because the frequency and effects of polymorphisms differ greatly by race .…”