Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults

Abstract

Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is one of the strongest diabetes loci identified to date; evidence suggests that it plays an important role in insulin secretion. Dietary factors that affect insulin demand might enhance the risk of diabetes associated with CDKAL1 variants. Our aim was to examine the interactions between dietary protein and fat intake and CDKAL1 genetic variants in relation to the risk of diabetes in Korean adults. Single nucleotide polymorphisms (SNPs) were selected with a genome-wide association study (GWAS) for diabetes after adjustment for age, gender, and examination site. Using data from the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), 3988 middle-aged Korean adults between 40–76 years of age (2034 men and 1954 women) were included in the study. Finally, rs7756992 located within the CDKAL1 gene region was selected from GWAS (p-value < 5 × 10−8). Multivariable logistic regression models were used to evaluate the interactions between genotypes and dietary protein and fat intake in relation to diabetes risk after adjustment for age, gender, BMI, waist circumference, physical activity, smoking status, drinking habits, and examination site. Significant interactions between CDKAL1 rs7756992 and dietary protein and fat intake for the risk of diabetes were observed in men (p-value < 0.05). In women, significant interactions between dietary protein and fat intake and CDKAL1 variants (rs7756992) were associated with increased risk of diabetes (p-value < 0.05). Dietary protein and fat intake interacted differently with CDKAL1 variants in relation to the risk of diabetes in Korean adults of both genders. These findings indicate that CDKAL1 variants play a significant role in diabetes and that dietary protein and fat intake could affect these associations.

Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes

“…We found associations between HTR2A rs6313 and emotional eating, as well as HTR1D rs623988 and CDKAL1 rs9295474 with external eating ( Table 1 ). CDKAL1 rs9295474 exhibited strong association with T2D in multi-ethnic cohorts from Southeast Asia [ 58 ], with its polymorphisms potentially affecting insulin resistance in response to varying levels of dietary fat and protein intake [ 59 ]. Moreover, CDKAL1 rs9295474 was notably associated with hypertension SBP and DBP in individuals of European ancestry [ 60 ].…”

Genome-Wide Association Study and Identification of Candidate Genes for Intramuscular Fat Fatty Acid Composition in Ningxiang Pigs

“…Twenty-five genes were annotated in the upstream and downstream regions of twentyone loci related to MUFAs. Among them, genes such as ALOX5AP [46], MEDAG [48], ISL1 [49], RXRB [50], CRY1 [51], and CDKAL1 [52] were found to be related to lipid synthesis and metabolism. Interestingly, ALOX5AP and MEDAG are two genes upstream and downstream of the MARC0099145 locus.…”