Association of polygenic risk scores for insulin resistance risk and their interaction with a plant-based diet, especially fruits, vitamin C, and flavonoid intake, in Asian adults

Abstract

Objectives: Insulin resistance is a common risk factor for metabolic syndrome (MetS), leading to type 2 diabetes mellitus and cardiovascular diseases. This study tested the hypothesis that the polygenic variants associated with the risk of insulin resistance (IR) interact with the lifestyles and nutrient intake of participants aged >40 in a large city hospital-based cohort (n = 58 701).

Methods: Polygenic risk score (PRS)-lifestyle interactions were evaluated. The participants were categorized into IR (case) and no IR (control) groups using a cutoff of a homeostasis model assessment of IR of 2.32, as estimated with a prediction model generated from the Ansan-Ansung cohort. Single-nucleotide polymorphism (SNP) with an SNP-SNP interaction influencing IR risk were identified using a genome-wide association study and generalized multifactor dimensionality reduction analysis after adjusting for IR-related variables. The selected genetic variants were confirmed in the Ansan-Ansung cohort.

Results: IR was associated mainly with body mass index by 14.24, fat mass by 4.57, and MetS by 8.10 times. Serum high-sensitive C-reactive protein, aspartate aminotransferase, and alanine aminotransferase concentrations were positively associated with IR risk. Plant-based diet (PBD), vitamin C (V-C), and flavonoid intakes were inversely associated with IR risk. The optimal model with SNP-SNP interaction included seven SNPs (CDKAL1_rs7754840, HNF4A_rs4812829, GCKR_rs780093, SLC30A8_rs11558471, KCNQ1_rs2237895, ANK2_rs12503758, and PTPRD_rs10977434) from generalized multifactor dimensionality reduction. After adjusting for the covariates, a high PRS of the seven-SNP model was positively associated with an IR risk of 1.78 times. The seven-SNP model interacted with the energy and PBD intake (especially, high in fruit, V-C and flavonoid). to influence IR risk. In the participants with low-energy, PBD, fruit, flavonoid, and V-C intakes, the percentage of high IR was higher in the high- than in the low-PRS group.

Conclusions: Adults having a high PRS for IR may benefit from a PBD containing high amounts of fruits, V-C, and flavonoids, which were found inversely related to IR risk. The results can be applied to personalized nutrition.

Keywords: Flavonoids; Insulin resistance; Metabolic syndrome; Plant-based diet; Polygenic risk scores; Vitamin C.