Open AccessCDKAL1 and HHEX are associated with type 2 diabetes‐related traits among Y up'ik people (在尤皮克人群中 CDKAL1 和 HHEX 与2型糖尿病相关特征有关)
Author(s) -
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.
Publication year - 2014
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12093
Subject(s) - single nucleotide polymorphism , genome wide association study , type 2 diabetes , snp , medicine , population , glucose homeostasis , body mass index , genetic association , diabetes mellitus , endocrinology , genetics , biology , insulin resistance , genotype , gene , environmental health
Background Genome‐wide association studies ( GWAS ) have identified single nucleotide polymorphisms ( SNPs ) associated with type 2 diabetes ( T2D ), mainly among individuals of E uropean ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D ‐related traits in an A laska N ative 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. Methods In 1144 Y up'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. Results The 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. Conclusion Our results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this A laska N ative population with a low prevalence of T2D , and suggest that these loci should be examined in greater detail in this population.