K C Chiu1, L M Chuang, A Chu, C Yoon. 1. Department of Medicine, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA. kchiu@mednet.ucla.edu
Abstract
BACKGROUND: An A54T polymorphism of the fatty acid binding protein 2 (FABP2) gene was found to be associated with insulin resistance in nondiabetic Pima Indians. Design This is a cross-sectional study to examine the role of this polymorphism in insulin resistance in 71 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S, ISI(M), ISI(S)) and beta-cell function (%B, dI/dG, 1stPHS, 2ndPHS) were estimated based on published models. Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotypes and phenotypes was examined. RESULTS: After genotyping, we identified 34 AA, 32 AT and five TT subjects. The TT subjects were pooled together with the AT subjects during the analysis due to their low number. No difference was noted in gender distribution, clinical features, or fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had lower %S and ISI(S) than the AA group (P = 0.0118 and P = 0.0170, respectively). The difference in ISI(M) was marginal (P = 0.0544). However, no difference was noted in beta-cell function between the two groups. Multivariate analysis revealed that this polymorphism was an independent but modest determinant for %S (P = 0.0149), ISI(M) (P = 0.0489) and ISI(S) (P = 0.0175). It independently contributed 6.04% (95% CI, 0.02-20.53%), 4.28% (95% CI, 0.08-17.63%) and 4.94% (95% CI, 0.01-18.75%) of the variation of %S, ISI(M) and ISI(S), respectively. CONCLUSIONS: We demonstrated that the A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population.
BACKGROUND: An A54T polymorphism of the fatty acid binding protein 2 (FABP2) gene was found to be associated with insulin resistance in nondiabetic Pima Indians. Design This is a cross-sectional study to examine the role of this polymorphism in insulin resistance in 71 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S, ISI(M), ISI(S)) and beta-cell function (%B, dI/dG, 1stPHS, 2ndPHS) were estimated based on published models. Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotypes and phenotypes was examined. RESULTS: After genotyping, we identified 34 AA, 32 AT and five TT subjects. The TT subjects were pooled together with the AT subjects during the analysis due to their low number. No difference was noted in gender distribution, clinical features, or fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had lower %S and ISI(S) than the AA group (P = 0.0118 and P = 0.0170, respectively). The difference in ISI(M) was marginal (P = 0.0544). However, no difference was noted in beta-cell function between the two groups. Multivariate analysis revealed that this polymorphism was an independent but modest determinant for %S (P = 0.0149), ISI(M) (P = 0.0489) and ISI(S) (P = 0.0175). It independently contributed 6.04% (95% CI, 0.02-20.53%), 4.28% (95% CI, 0.08-17.63%) and 4.94% (95% CI, 0.01-18.75%) of the variation of %S, ISI(M) and ISI(S), respectively. CONCLUSIONS: We demonstrated that the A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population.
Authors: Coleen M Damcott; Eleanor Feingold; Susan P Moffett; M Michael Barmada; Julie A Marshall; Richard F Hamman; Robert E Ferrell Journal: Hum Genet Date: 2003-03-13 Impact factor: 4.132