Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes.

摘要: Abstract The functional knockout of the calcium-sensitive, nonselective cation channel TRPM5 alters glucose-induced insulin secretion and glucose tolerance. We hypothesized that genetic variation in gene may contribute to prediabetic phenotypes, including pancreatic β-cell dysfunction. genotyped 1798 white subjects at increased type 2 diabetes mellitus risk for 9 single nucleotide polymorphisms (namely, rs2301696, rs800344, rs800345, rs800347, rs800348, rs2074234, rs2301698, rs886277, rs2301699) also performed correlational analyses with metabolic traits. An oral tolerance test (OGTT) was conducted on all subjects, a subset (n = 525) additionally underwent hyperinsulinemic-euglycemic clamp. chosen cover 100% common (minor allele frequency ≥0.05) within locus (D' 1.0; r² ≥ 0.8). Rs800344, rs2301699 were significantly associated area under curve (AUC) during OGTT additive dominant models after adjustment sex, age, body mass index (all Ps ≤ .0025). Furthermore, rs800344 2-hour model (P .0009). After stratification ratio AUC 0 30 minutes women .0097), but not men .3), model. Female minor carriers showed lower glucagon-like peptide–1 levels compared major homozygotes .0124), whereas male no significant differences found .3). In our German population, variants are likely be phenotypes; this turn development mellitus.