Impact of Apolipoprotein A5 Polymorphisms on Insulin Sensitivity and Beta -Cell Function

Objectives: Alternation in lipid metabolism can affect both insulin sensitivity and [beta]-cell function. Apolipoprotein A5 (APOA5) is an important determinant of lipid metabolism. The impact of the APOA5 gene on insulin sensitivity and [ beta]-cell function has not been examined. Methods: We examined the influence of 2 amino acid polymorphisms (V150M and G182C) in the APOA5 gene on insulin sensitivity and [ beta]-cell function in 67 glucose-tolerant white subjects. Insulin sensitivity index (ISI) and first- and second-phase insulin responses (1stIR and 2ndIR) were assessed using a hyperglycemic clamp technique. Results: We identified 59 VV and 8 VM subjects, and none had either the GC or CC genotype . Although no association was found with fasting lipid profile and plasma glucose concentrations during oral glucose tolerance test, the V150M was associated with higher 1stIR (P = 0.0010) and 2ndIR (P = 0.0016) and lower ISI (P = 0.0135). The associations of this polymorphism with 1stIR (P = 0 .0081) and 2ndIR (P = 0.0087) were independent of sex, age, and body mass index, but not ISI. Conclusions: The V 150M polymorphism had an independent influence on 1stIR and 2ndIR. Although the biologic consequence of this polymorphism remains to be determined, the V150M polymorphism in the APOA5 gene is a genetic marker for [beta ]-cell function.