Linkage of serum insulin concentrations to chromosome 3p in Mexican Americans

Hyperinsulinemia predicts the development of type 2 diabetes, and family st udies suggest that insulin levels are regulated in part by genes, We conduc ted a genome-wide scan to detect genes influencing variation in fasting ser um insulin concentrations in 391 nondiabetic individuals from 10 large mult igenerational families. Approximately 380 microsatellite markers with an av erage spacing of 10 cM were genotyped in all study subjects, Insulin concen trations measured by radioimmunoassay were transformed by their natural log arithms before analysis, In multipoint analysis, peak evidence for linkage occurred on chromosome 3p similar to 109 cM from pter in the region of 3p14 .2-p14.1. The multipoint logarithm of odds (LOD) score was 3.07, occurring in the region flanked by markers D3S1600 and D3S1285 (P value by simulation <0.0001), In a two-point analysis, LOD scores ranged from 0.75 to 2.52 for the nine markers typed in the region spanning 88-143 cM from pter The fast ing insulin resistance index was highly correlated with fasting insulin con centrations in this sample and also provided strong evidence for linkage to this region (LOD = 2.99). There was no evidence in our genome-wide scan fo r linkage of insulin levels to any other chromosome. These results provide evidence that a gene-influencing variation in insulin concentrations exists on chromosome 3p, Possible candidate genes in this region include GBE1 and ACOX2, which encode enzymes involved in glycogen and fatty acid metabolism , respectively.