Low HDL concentration in rs2048327-G carriers can predispose men to develop coronary heart disease: Tehran Cardiometabolic genetic study (TCGS)

Gene. 2021 Apr 30:778:145485. doi: 10.1016/j.gene.2021.145485. Epub 2021 Feb 11.

Abstract

Recent genome-wide association studies (GWAS) highlighted the importance of genetic variations on SLC22A3 and MIA3 genes in developing coronary heart disease (CHD) among different ethnicities. However, the influence of these variations is not recognized within the Iranian population. Hence, in the present study, we aim to investigate two key single nucleotide polymorphisms (SNPs) on CHD incidence in this population. For this purpose, from Tehran Cardiometabolic Genetic Study (TCGS), 453 individuals with CHD were selected as a case and 453 individuals as a control that matched their age and gender. After quality control of two selected SNPs, rs2048327 (SLC22A3) and rs17465637 (MIA3), we used genotyps resulted from chip-typing technology and conducted the logistic regression analysis adjusted for non-genetic risk factors to detect the possible association of these SNPs with the CHD development. Our findings demonstrated the rs2048327-G and rs17465637-C can significantly increase the risk of CHD development about two times in only males and females, respectively. Interestingly, in the male carriers of the risk allele (G) of rs2048327, the low high-density lipoprotein (HDL) level can significantly predispose them to develop coronary heart disease in the future. According to our results, paying more attention to gender and genetic markers can help more efficient coronary heart disease screening and diagnosis.

Keywords: Coronary heart disease (CHD); MIA3; SLC22A3; Single nucleotide polymorphism (SNP).

MeSH terms

  • Aged
  • Aryl Hydrocarbon Receptor Nuclear Translocator / genetics*
  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Iran
  • Logistic Models
  • Male
  • Middle Aged
  • Organic Cation Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • ARNT protein, human
  • Cholesterol, HDL
  • Organic Cation Transport Proteins
  • solute carrier family 22 (organic cation transporter), member 3
  • Aryl Hydrocarbon Receptor Nuclear Translocator