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Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.

Abstract：

AIMS/HYPOTHESIS:Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan. METHODS:CREBRF rs12513649 and rs373863828 were genotyped in 2022 participants in a community-based cross-sectional study designed to identify determinants of diabetes and end-stage renal disease (ESRD). Associations were analysed with adjustment for age, sex, ESRD and the first four genetic principal components from a genome-wide association study (to account for population stratification); a genomic control procedure was used to account for residual stratification. RESULTS:The G allele at rs12513649 had an overall frequency of 7.7%, which varied from 2.2% to 20.7% across different Marianas and Micronesian populations; overall frequency of the A allele at rs373863828 was 4.2% (range: 1.1-5.4%). The G allele at rs12513649 was associated with higher BMI (β = 1.55 kg/m2 per copy; p = 0.0026) as was the A allele at rs373863828 (β = 1.48 kg/m2, p = 0.033). The same alleles were associated with lower risk of diabetes (OR per copy: 0.63 [p = 0.0063] and 0.49 [p = 0.0022], respectively). Meta-analyses combining the current results with previous results in Polynesians showed a strong association between the A allele at rs373863828 and BMI (β = 1.38 kg/m2; p = 2.5 × 10-29) and diabetes (OR 0.65, p = 1.5 × 10-13). CONCLUSIONS/INTERPRETATION:These results confirm the associations of CREBRF variants with higher BMI and lower risk of diabetes and, importantly, they suggest that these variants contribute to the risk of obesity and diabetes in Oceanic populations.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Hanson RL,Safabakhsh S,Curtis JM,Hsueh WC,Jones LI,Aflague TF,Duenas Sarmiento J,Kumar S,Blackburn NB,Curran JE,Mahkee D,Baier LJ,Knowler WC,Nelson RG

doi

10.1007/s00125-019-4932-z

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

1647-1652

issue

eissn

0012-186X

issn

1432-0428

pii

10.1007/s00125-019-4932-z

journal_volume

pub_type

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Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan.