CDKAL1 and HHEX are associated with type 2 diabetes‐related traits among Yup'ik people (在尤皮克人群中CDKAL1和HHEX与2型糖尿病相关特征有关)

Abstract

Background: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type-2 diabetes (T2D), mainly among individuals of European ancestry. 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 (n-3 PUFA) intake, modify these associations. Methods: In 1,144 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, 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 HOMA-B (p=0.0014). The GRS is significantly associated with FG and combined FG & 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 Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.

High genetic risk scores for impaired insulin secretory capacity doubles the risk for type 2 diabetes in Asians and is exacerbated by Western‐type diets

“…Each risk allele of the 10 selected SNPs contributed to increasing the risk of T2DM by 1.111 to 1.293 folds. In a European‐American population KCNQ1 rs163177 had a positive association with T2DM risk . However, KCNQ1 rs163177 has not been reported to be associated with T2DM in Asians, including Chinese.…”

Stable Isotope Ratios as Biomarkers of Diet for Health Research

“…However, as a validated biomarker of marine food (fish and marine mammal) intake for the Yup’ik population of SW Alaska, the RBC δ 15 N value has been used to examine how gene × diet interactions are associated with risk factors for obesity and chronic disease (2, 71, 81, 82), and it was recently used to demonstrate that high and low consumers of marine foods exhibit very different patterns of gene methylation (3). We found that the RBC δ 15 N value captured most of the same diet - risk factor associations that were previously identified for Yup’ik people using RBC EPA and DHA (84), but that in addition, high RBC δ 15 N values were associated with high adiponectin, which promotes insulin sensitivity, and were inversely associated with blood pressure (102).…”

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus

“…Additionally, the HHEX gene rs5015480 C allele was significantly associated with increased fasting glucose and HbA 1c levels (29). Additionally, the HHEX gene rs5015480 C allele was significantly associated with increased fasting glucose and HbA 1c levels (29).…”