Genetic Variability in eIF2 α Gene Is Associated with Islet β -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 ( eIF2α ) pathway mutations lead to failure of β -cell function. The aim of this article was to assess the association between eIF2α and the risk of glucose metabolism abnormalities.

Methods: Two eIF2α 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 β -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 ΔI30/ΔG30 and ΔI120/ΔG120 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/m2 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 eIF2α polymorphism is associated with islet β -cell function in a Chinese population.