Genetic Risk Score of Nine Type 2 Diabetes Risk Variants that Interact with Erythrocyte Phospholipid Alpha-Linolenic Acid for Type 2 Diabetes in Chinese Hans: A Case-Control Study

Modulation of n-3 fatty acids on genetic susceptibility to type 2 diabetes (T2D) is still not clear. In a case-control study of 622 Chinese T2D patients and 293 healthy controls, a genetic risk score (GRS) was created based on nine T2D genetic variants. Logistic regression was used to examine the interaction of the GRS with erythrocyte phospholipid n-3 fatty acids for T2D risk. Every 1-unit (corresponding to 1 risk allele) increase in GRS was associated with 12% (Odds ratio (OR): 1.12; 95% confidence intervals (CI): 1.04-1.20) higher risk of T2D. Compared with the lowest quartile, participants had lower T2D risk in the 2nd (OR: 0.55; 95% CI: 0.36-0.84), 3rd (OR: 0.58; 95% CI: 0.38-0.88) and 4th (OR: 0.67; 95% CI: 0.44-1.03) quartile of alpha-linolenic acid (ALA) levels. Significant interaction (p-interaction = 0.029) of GRS with ALA for T2D risk was observed. Higher ALA levels were associated with lower T2D risk only among participants within the lowest GRS tertile, with ORs 0.51 (95% CI: 0.26-1.03), 0.44 (95% CI: 0.22-0.89) and 0.49 (95% CI: 0.25-0.96) for the 2nd, 3rd and 4th ALA quartile, compared with the 1st. This study suggests that higher erythrocyte ALA levels are inversely associated with T2D risk only among participants with low T2D genetic risk, with high genetic risk abolishing the ALA-T2D association.