CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik people.

• Main Authors: Klimentidis, Yann C, Lemas, Dominick J, Wiener, Howard H, O'Brien, Diane M, Havel, Peter J, Stanhope, Kimber L, Hopkins, Scarlett E, Tiwari, Hemant K, Boyer, Bert B
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: eScholarship, University of California 2014
• Subjects: Humans; Diabetes Mellitus; Type 2; Genetic Predisposition to Disease; Insulin; tRNA Methyltransferases; Blood Glucose; Fatty Acids; Omega-3; Homeodomain Proteins; Transcription Factors; Body Mass Index; Diet; Fasting; Prevalence; Linear Models; Risk Factors; Gene Frequency; Genotype; Polymorphism; Single Nucleotide; Adult; Middle Aged; Inuits; Alaska; Female; Male; Cyclin-Dependent Kinase 5; Young Adult; Glycated Hemoglobin A; Alaska Native; glycemic traits; n-3 polyunsaturated fatty acids; type 2 diabetes single nucleotide polymorphisms; 阿拉斯加原住民，血糖特征，n-3多不饱和脂肪酸，2型糖尿病单核苷酸多态性; n-3; 2; Hemoglobin A; Glycosylated; Clinical Sciences; Public Health and Health Services; inuits; Yup'ik
• Online Access: https://escholarship.org/uc/item/6wx45211

BackgroundGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations.MethodsIn 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score (GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index (BMI), and n-3 PUFA intake.ResultsThe rs7754840 SNP in CDKAL1 is significantly associated with HbA1c (P = 0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose (FG) and HbA1c measure (P = 0.00046) and with homeostatic model assessment of β-cell function (HOMA-B; P = 0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEX SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake.ConclusionOur results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.