Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case-control study

Abstract

Sex hormone binding globulin (SHBG) level is positively associated with the high-density lipoprotein cholesterol (HDL-C) levels. The aim of this study was to investigate the effects of the SHBG gene variations (D356N, rs1799941, and P156L) on SHBG and HDL-C levels and Coronary Heart Disease (CHD) risk. The SHBG D356N (rs6259,G>A), P156L (rs6258,C>T), and rs1799941(G>A) polymorphisms were determined in 131 male CHD patients and 55 male controls by PCR-RFLP and real-time PCR techniques. SHGB levels were measured by Electro-chemiluminescence immunoassay (ECLIA). In the patients who had SHBG levels lower than threshold 35nmol/l value, the risk of being HDL-C levels lower than threshold 0.90mmol/l value was observed statistically significant (p=0.017; OR 2.522, 95% CI 1.170-5.438). The rs1799941 GG was associated with increased CHD risk when compared with the A allele carriers (GA+AA) (p=0.019, OR 2.222, 95% CI 1.130-4.371). In addition, the rs1799941 GG genotype and D356NN allele were associated with lower SHBG in the CHD group (p<0.01). The logistic regression analysis also revealed the rs1799941 GG genotype was significantly associated with low SHBG in CHD patients. It was observed that Haplotype-1(rs1799941 G allele-P156L P allele-D356N D allele) was associated with increased CHD risk, while Haplotype-2 (rs1799941 rare A allele-P156L C allele- D356N G allele) was correlated with the decreased CHD risk (p=0.0167). Our findings suggest that there is a positive correlation between SHBG and HDL-C levels in CHD patients, and this association might be affected by SHBG gene variations.