Key Findings:
Prevalence of type 2 diabetes (T2D) is increasing globally, especially among developing countries, gaining higher public health priority for its prevention. Genome-wide interaction of genotype by erythrocyte n-3 fatty acids has significant variance contributions for T2D traits, such as insulin resistance, fasting insulin and glucose. The aim of the present study was to investigate the interaction of erythrocyte phospholipid marine and plant-based n-3 fatty acid with GRS, created based on several established T2D variants among East Asians, for T2D risk. Here, erythrocyte phospholipid ALA interacted with unweighted GRS to modulate the risk of T2D in a Chinese population. The inverse association between erythrocyte phospholipid ALA and T2D only existed among individuals with low T2D genetic risk, but did not exist among those with high T2D genetic risk. No interactions of GRS with marine n-3 fatty acids in the present study were found. The interaction between erythrocyte phospholipid ALA and T2D GRS suggests that, in order to prevent T2D, it may be more efficient to increase dietary intake of ALA in participants with lower T2D genetic risk. However, given the solid evidence of the beneficial associations of higher dietary/blood ALA with lower T2D and CVD, participants with low ALA status are recommended to increase dietary ALA intake regardless of their genetic profiles.
ABSTRACT
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.
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