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Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

ABSTRACT: BACKGROUND:Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake. METHODS:We searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup'ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the ?15N value. RESULTS:We identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the ?15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes. CONCLUSION:We provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.

SUBMITTER: Aslibekyan S

PROVIDER: S-EPMC4971612 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

Aslibekyan Stella S Vaughan Laura K LK Wiener Howard W HW Hidalgo Bertha A BA Lemas Dominick J DJ O'Brien Diane M DM Hopkins Scarlett E SE Stanhope Kimber L KL Havel Peter J PJ Thummel Kenneth E KE Boyer Bert B BB Tiwari Hemant K HK

Genes & nutrition 20160802

<h4>Background</h4>Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered ...[more]

PMID: 27579147

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Project description:BackgroundThe relationship between dietary n-3 PUFAs and the prevention of cardiometabolic diseases, including type 2 diabetes, is unresolved. Examination of the association between n-3 PUFAs and chronic low-grade inflammation in a population where many individuals have had an extremely high intake of marine mammals and fish throughout their lifespan may provide important clues regarding the impact of n-3 PUFAs on health.ObjectivesThe aim of this study was to explore associations between concentrations of n-3 PUFAs resulting from habitual intake of natural food sources high in fish and marine mammals with immune biomarkers of metabolic inflammation and parameters of glucose regulation.MethodsA total of 569 Yup'ik Alaska Native adults (18-87 years old) were enrolled in this cross-sectional study between December 2016 and November 2019. The RBC nitrogen isotope ratio (NIR; 15N/14N) was used as a validated measure of n-3 PUFA intake to select 165 participant samples from the first and fourth quartiles of n-3 PUFA intakes. Outcomes included 38 pro- and anti-inflammatory cytokines and 8 measures of glucose homeostasis associated with type 2 diabetes risks. These outcomes were evaluated for their associations with direct measurements of EPA, DHA, and arachidonic acid in RBCs.AnalysisLinear regression was used to detect significant relationships with cytokines and n-3 PUFAs, adiposity, and glucose-related variables.ResultsThe DHA concentration in RBC membranes was inversely associated with IL-6 (β = -0.0066; P < 0.001); EPA was inversely associated with TNFα (β = -0.4925; P < 0.001); and the NIR was inversely associated with Monocyte chemoattractant protein-1 (MCP-1) (β = -0.8345; P < 0.001) and IL-10 (β = -1.2868; P < 0.001).ConclusionsHabitual intake of marine mammals and fish rich in n-3 PUFAs in this study population of Yup'ik Alaska Native adults is associated with reduced systemic inflammation, which may contribute to the low prevalence of diseases in which inflammation plays an important role.

Project description:BackgroundAlaska Native people currently have a higher prevalence of hypertension than do nonnative Alaskans, although in the 1950s hypertension was rare among Alaska Native people. A novel biomarker of marine foods, the nitrogen isotope ratio (δ¹⁵N) in RBCs was shown to be negatively associated with systolic and diastolic blood pressure. Few studies have examined how individual characteristics modify the association of marine food intake with blood pressure.ObjectiveThis exploratory analysis examined whether sex, adiposity, and hypertension modify the inverse association between marine food intake and blood pressure.MethodsWe used covariate-adjusted linear models to describe the association between δ¹⁵N and blood pressure in 873 adult Alaska Native (Yup'ik) people who resided in 8 communities in southwest Alaska. We separately stratified by sex, body mass index (BMI) group, abdominal obesity, and hypertension status and assessed the interaction between δ¹⁵N and participant characteristics on blood pressure via likelihood ratio tests.ResultsThe association between δ¹⁵N and systolic blood pressure was modified by sex, BMI status, and abdominal obesity, with the inverse association observed only in the male (β = -1.5; 95% CI: -2.4, -0.6 : , nonobese BMI (β = -1.7; 95% CI: -2.5, -1.0), and non-abdominally obese (β = -1.6; 95% CI: -2.4, -0.9) strata (all P-interaction < 0.0001). A reduction in diastolic blood pressure associated with δ¹⁵N was observed in the nonobese BMI (β = -1.1; 95% CI: -1.7, -0.5) and non-abdominally obese (β = -1.1; 95% CI: -1.7, -0.5) strata, although only the interaction between BMI group and δ¹⁵N with diastolic blood pressure was significant. The inverse association between δ¹⁵N and both systolic and diastolic blood pressure was observed in nonhypertensive individuals, although the comparison had limited power. The results were consistent with those identified by using combined RBC concentrations of eicosapentaenoic acid and docosahexaenoic acid as the biomarker of marine food intake, although the associations identified by using δ¹⁵N were larger.ConclusionsObesity status modified the inverse association between marine food intake and both systolic and diastolic blood pressure in adult Alaska Native (Yup'ik) people. The inverse association between δ¹⁵N and systolic blood pressure was also modified by sex.

Dataset Information

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

Publications

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

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