Genetic Variability In Eif2 Alpha Gene Is Associated With Islet Beta-Cell Function In The Development Of Diabetes In A Chinese Han Population

Aims. Protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2 alpha) pathway mutations lead to failure of beta-cell function. The aim of this article was to assess the association between eIF2a and the risk of glucose metabolism abnormalities. Methods. Two eIF2a SNPs (rs9840992 T>C and rs13072593 A>G) were selected based on CHB data from HapMap, and 1466 unrelated nondiabetes individuals were genotyped. All subjects were examined by the 75 g oral glucose tolerance test, and 733 participated in a subsequent insulin release test. Various indicators of insulin resistance and islet beta-cell function were examined. Results. There were no significant differences in genotype distribution and allele frequency between the prediabetes and controls. CC genotype carriers at rs9840992 showed higher insulin levels at 120 min after a 75 g glucose load than noncarriers. Also, CC homozygotes had higher Delta I30/Delta G30 and Delta I120/Delta G120 than noncarriers, even after adjusting for insulin resistance. CC homozygotes had greater AUCi values than noncarriers. Subjects aged >= 65 yrs, those with a BMI >= 24 kg/m(2) and those carrying the rs9840992 risk allele, had a 2.5-fold higher risk of glucose abnormalities than subjects who had none of these risk factors. Conclusion. The eIF2 alpha polymorphism is associated with islet beta-cell function in a Chinese population.