The MTMR9 rs2293855 polymorphism is associated with glucose tolerance, insulin secretion, insulin sensitivity and increased risk of prediabetes

Gene. 2014 Aug 10;546(2):150-5. doi: 10.1016/j.gene.2014.06.028. Epub 2014 Jun 14.

Abstract

Background: Polymorphism of rs2293855 in gene MTMR9 has been associated with obesity and metabolic syndrome. We aim to study the association of rs2293855 with type 2 diabetes mellitus (T2DM) intermediate phenotypes in a Han Chinese population.

Methods: The polymorphism was genotyped in 838 Han Chinese individuals using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS); all participants underwent a 75 g oral glucose tolerance test (OGTT); associations between the polymorphism and glucose tolerance, indices of insulin secretion and indices of insulin sensitivity were analyzed.

Results: The frequency of genotypes and alleles differed significantly between normal glucose tolerance and prediabetes (P=0.043 and P=0.009, respectively). The GG homozygous presented higher fasting plasma glucose (P=0.009), higher 2-hour plasma glucose (P=0.024) and higher glucose area under the curve (AUC, P=0.01). Moreover, the G allele of rs2293855 was associated with glucose intolerance (fasting glucose, P=0.012; glucose AUC, P=0.006; 2-h glucose, P=0.024); it is also associated with decreased indices of insulin sensitivity (fasting insulin, P=0.043; insulin sensitivity index composite, P=0.009; homeostasis model assessment of insulin resistance, HOMA-IR, P=0.008) and decreased indices of insulin secretion (HOMA of beta cell function, HOMA-B, P=0.028; insulinogenic index, P=0.003). In addition, the minor allele G was also associated with increased risk of prediabetes (OR=1.463, 95%CI: 1.066-2.009, P=0.018).

Conclusions: Polymorphism of rs2293855 in MTMR9 is associated with measures of glucose tolerance, indices of insulin secretion and indices of insulin sensitivity. We also suggest that allele G is likely to increase the risk of prediabetes by influencing both insulin secretion and insulin sensitivity.

Keywords: Genetic; MTMR9; OGTT; Prediabetes; rs2293855.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian Continental Ancestry Group
  • China
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / metabolism
  • Female
  • Glucose Tolerance Test
  • Glucose*
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance / genetics*
  • Insulin Secretion
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Risk Factors

Substances

  • Insulin
  • MTMR9 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Glucose