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

Mol Biol Rep. 2019 Aug;46(4):4259-4269. doi: 10.1007/s11033-019-04880-x. Epub 2019 May 20.

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 D356 N (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 35 nmol/l value, the risk of being HDL-C levels lower than threshold 0.90 mmol/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 D356 N N 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-D356 N D allele) was associated with increased CHD risk, while Haplotype-2 (rs1799941 rare A allele-P156L C allele- D356 N 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.

Keywords: CHD; Gene; HDL-C; Polymorphism; SHBG.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cholesterol, HDL / genetics
  • Coronary Disease / genetics*
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Hormone-Binding Globulin / genetics*
  • Sex Hormone-Binding Globulin / metabolism

Substances

  • Cholesterol, HDL
  • SHBG protein, human
  • Sex Hormone-Binding Globulin