Genetic susceptibility to pre diabetes mellitus and related association with obesity and physical fitness components in Mexican-Mestizos

Prim Care Diabetes. 2018 Oct;12(5):416-424. doi: 10.1016/j.pcd.2018.07.005. Epub 2018 Jul 21.

Abstract

Pre diabetes mellitus (pre-DM) is considered an early-reversible condition that can progress to Type 2 diabetes mellitus (T2DM) which is the main cause of death for adult Mexican population. Gene variants influencing fasting glucose levels may constitute helpful tool for prevention purposes in pre-DM condition. Physically active Mexican-Mestizo adults (n=565) were genotyped for 6 single nucleotide polymorphisms (SNPs) (ADIPOQ rs2241766, ACSL1 rs9997745, LIPC rs1800588, PPARA rs1800206, PPARG rs1801282 and PPARGC1A rs8192678) related to lipid and carbohydrate metabolism. Fasting glucose was measured and values classified as pre-DM (≥100mg/dL) or normal fasting glucose. Logistic models were used to test associations between pre-DM condition and SNPs, and interaction with Body Mass Index (BMI) and physical fitness components. The A allele of ASCL1 rs9997745 conferred increased risk (OR=3.39, p=0.001) of pre-DM which is modulated by BMI. The A allele of the PPARGC1A rs8192678 showed significant SNP*BMI (OR=1.10, p=0.008) interaction effect for pre-DM risk, meaning that obese subjects showed higher pre-DM risk but normal weight subjects showed lower risk. The effect increased with age and was attenuated by higher cardiorespiratory values. We found that both ACSL1 rs9997745 and PPARGC1A rs8192678 are associated with pre-DM, and that BMI significantly modified their association.

Keywords: Genetic susceptibility; Gene–environment interaction; Pre-diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / genetics*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Case-Control Studies
  • Coenzyme A Ligases / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Health Status
  • Humans
  • Indians, North American / genetics*
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Obesity / diagnosis
  • Obesity / ethnology
  • Obesity / genetics*
  • Obesity / physiopathology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
  • Phenotype
  • Physical Fitness*
  • Polymorphism, Single Nucleotide*
  • Prediabetic State / diagnosis
  • Prediabetic State / ethnology
  • Prediabetic State / genetics*
  • Prediabetic State / physiopathology
  • Risk Factors
  • Young Adult

Substances

  • Blood Glucose
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Coenzyme A Ligases
  • ACSL1 protein, human