Genetic variants of ALOXs genes in polyunsaturated fatty acid / arachidonic acid metabolism associated with type-2 diabetes development

Poly-unsaturated fatty acids (PUFAs)/arachidonic acids (AAs) and their derived eicosanoids play potent roles in triggering inflammation during obesity and diabetes development. Recent studies have indicated functional roles of ALOX5, ALOX12, ALOX12B, and ALOX15 in the development of insulin resistance and islet β-cell dysfunction. However, the impact of their genetic variants on type 2 diabetes (T2D) development in Asian patients remains unclear. In this study, 1,682 healthy controls and 788 patients with T2D were enrolled for genotyping those four ALOX genes by the TaqMan method. A total of eight Han Chinese-specific SNPs (two SNps for each gene) were selected for this study. Of the SNPs tested, genetic variations in ALOX12 (rs312462) and ALOX12B (rs.4792199 and rs.4792216) were found to be significantly associated with T2D development. Multivariable regression analysis further revealed the genetic variation at rs.4792199 as a potential independent marker as age (older than 52) or BMI (higher than 25) for T2D prognosis. When T2D patients were stratified according to age and BMI, SNPs in both ALOX12 (rs312462) and ALOX12B (rs.4792199 and rs.4792216) showed significant impact on T2D development. The present study confirms the involvement of ALOX12 and ALOX12B genetic variants in conferring susceptibility to T2D development, possibly though alterations in PUFA/AA metabolism.