Association between an ASIC3 gene variant and insulin resistance in Taiwanese

Background: Acid-sensing ion channel 3 (ASIC3) is a ligand-gated cation channel activated by extracellular protons. ASIC3^-/- mice exhibit protection against age-dependent glucose intolerance with enhanced insulin sensitivity. Methods: To determine the association between ASIC3 genetic polymorphisms and insulin resistance in Taiwanese, 606 unrelated subjects with no history of cardiovascular disease were recruited during routine health examinations. Results: Six ASIC3 gene polymorphisms were genotyped and only the rs2288646 polymorphism was found associated with insulin resistance. Significantly lower fasting serum insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) index and significantly higher quantitative insulin sensitivity check index (QUICKI) were observed in subjects carrying the rs2288646-. A allele than in the non-carriers (P=0.028, P=0.047 and P=0.031, respectively) after adjustment for age, gender, and body mass index (BMI). Significantly lower frequencies of the rs2288646-. A-containing genotypes were found in insulin resistant subjects (P=0.023). By multivariate analysis, rs2288646 genotypes, age, BMI, fasting plasma glucose level, C-reactive protein level, and soluble intercellular adhesive molecule 1 level, were all independently associated with HOMA-IR index and QUICKI (all, P<0.05). Conclusions: Our analysis indicated an independent association between an ASIC3 genetic polymorphism and insulin resistance in Taiwanese.