Identification of a TMEM182 rs141764639 polymorphism associated with central obesity by regulating tumor necrosis factor-α in a Korean population

J Diabetes Complications. 2020 Dec;34(12):107732. doi: 10.1016/j.jdiacomp.2020.107732. Epub 2020 Sep 6.

Abstract

Aims: To investigate the effect of a single nucleotide polymorphism (SNP) in transmembrane protein 182 (TMEM182) on the risk of having central obesity and the related phenotype.

Methods: In total, 2141 subjects with central obesity (n = 827) and normal controls (n = 1314) were included. The most strongly associated SNPs were related to waist circumference, and one SNP, rs141764639, was identified in TMEM182 (p = 7.30E-06, q = 0.0326).

Results: The TC genotype was associated with more central obesity; higher levels of blood pressure, glucose-related parameters, and inflammatory markers; abnormal lipid profiles; and smaller LDL particle sizes than the major allele homozygotes in the total population. TNF-α in the TC genotype showed extremely high levels compared to the TT genotype. There were significant interactions between the genotypes and waist circumference in relation to LDL particle size, TNF-α level, and IL-6 level. Compared with the reference group, the odds ratio for central obesity in C allele carriers was significantly increased by 2-fold.

Conclusions: The polymorphism of TMEM182 rs141764639 might have an effect on the incidence of central obesity in the Korean population by interacting with the upregulation of TNF-α, a proinflammatory cytokine. Moreover, LDL particle size, which is an atherogenic lipid profile trait, was associated with the TMEM182 rs141764639 genotype.

Keywords: Central obesity; LDL particle size; Polymorphism; TMEM182; Tumor necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genotype
  • Humans
  • Lipids / blood
  • Membrane Proteins / genetics*
  • Obesity, Abdominal* / epidemiology
  • Obesity, Abdominal* / genetics
  • Polymorphism, Single Nucleotide
  • Republic of Korea
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Lipids
  • Membrane Proteins
  • TMEM182 protein, human
  • Tumor Necrosis Factor-alpha