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.

Ju-Sheng Zheng,Duo Li,Jianqin Sun,Danfeng Xu,Hua Xie,Kelei Li,Tao Huang,Yanqiu Chen

doi:10.3390/nu9040376

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.

Highlights

Prevalence of type 2 diabetes (T2D) is increasing globally, especially among developing countries, gaining higher public health priority for its prevention [1]
In addition to age and sex in the primary interaction analysis; (2) We examined the interaction of weighted genetic risk score (GRS) with erythrocyte fatty acids for T2D risk, in order to investigate the influence of different weights/effect sizes of the SNPs on the results; (3) We examined the interaction of original unweighted
We found that erythrocyte phospholipid alpha-linolenic acid (ALA) interacted with unweighted

Summary

Introduction

Prevalence of type 2 diabetes (T2D) is increasing globally, especially among developing countries, gaining higher public health priority for its prevention [1]. Evidence from several randomized controlled trials suggests that physical activity and dietary intervention could prevent or delay progression of T2D [2,3,4]. T2D is subject to genetic predisposition, with more than 70 genetic loci being identified [5]. Emerging evidence indicates that interaction of genetic variants with diet or lifestyle may play an important role in the development of T2D [6,7]. Genome-wide interaction of genotype by erythrocyte n-3 fatty acids has significant variance contributions for. One previous study suggests that erythrocyte total n-3 fatty acids interact with genetic variant at PEPD gene

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