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Diabetologia

, Volume 61, Issue 7, pp 1603–1613 | Cite as

Discordant association of the CREBRF rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand

  • Mohanraj Krishnan
  • Tanya J. Major
  • Ruth K. Topless
  • Ofa Dewes
  • Lennex Yu
  • John M. D. Thompson
  • Lesley McCowan
  • Janak de Zoysa
  • Lisa K. Stamp
  • Nicola Dalbeth
  • Jennie Harré Hindmarsh
  • Nuku Rapana
  • Ranjan Deka
  • Winston W. H. Eng
  • Daniel E. Weeks
  • Ryan L. Minster
  • Stephen T. McGarvey
  • Satupa’itea Viali
  • Take Naseri
  • Muagututi’a Sefuiva Reupena
  • Phillip Wilcox
  • David Grattan
  • Peter R. Shepherd
  • Andrew N. Shelling
  • Rinki Murphy
  • Tony R. Merriman
Article

Abstract

Aims/hypothesis

The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Methods

Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis.

Results

For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p = 4.8 × 10−6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p = 1.9 × 10−6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p = 0.13), and nor was there evidence for associations with serum urate (β = 0.012 mmol/l, pcorrected = 0.10), gout (OR 1.00, p = 0.98) or CKD (OR 0.91, p = 0.59).

Conclusions/interpretation

Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.

Keywords

Association BMI CREBRF Genetic Māori Obesity Pacific Polynesian Type 2 diabetes 

Abbreviations

AIC

Akaike’s information criterion

CKD

Chronic kidney disease

CREB3

cAMP-responsive element binding protein 3

CREBRF

cAMP-responsive element binding protein 3 regulatory factor

MAF

Minor allele frequency

Notes

Acknowledgements

The authors sincerely thank the participants for generously donating their time and information to this study. The authors would like to thank J. Drake (Department of Rheumatology, Canterbury District Health Board, Christchurch, New Zealand), J. de Kwant, R. Laurence, C. Franklin and M. House (all Department of Medicine, University of Auckland, Auckland, New Zealand), N. Aupouri, R. Akuhata and C. Ford (all of Ngāti Porou Hauora Charitable Trust, Te Puia Springs, New Zealand) and G. Sexton (Counties Manukau District Health Board, Auckland, New Zealand) for recruitment.

Contribution statement

MK, TJM, PRS, RM and TRM contributed to the design of the study. OD, LM, JdZ, LKS, ND, JHH, NR, TN, MSR, RD, STM and SV contributed to data collection, and RKT, LY, JMDT, WWHE, DEW, RLM, PW, DG and ANS contributed to data analysis and interpretation. MK, RM and TRM drafted the manuscript and all of the other authors reviewed it. The manuscript was approved by all authors. TRM is the guarantor of this work.

Funding

The Health Research Council of New Zealand (grant no. 08/075, 10/548, 11/1075, 14/527) and the Maurice Wilkins Centre funded the New Zealand component of this study, and the National Institutes of Health funded the Samoa and American Samoa components (grant no. R01-HL093093 and R01-HL133040).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4623_MOESM1_ESM.pdf (872 kb)
ESM (PDF 872 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mohanraj Krishnan
    • 1
    • 2
  • Tanya J. Major
    • 3
  • Ruth K. Topless
    • 3
  • Ofa Dewes
    • 4
  • Lennex Yu
    • 5
  • John M. D. Thompson
    • 1
    • 6
  • Lesley McCowan
    • 1
  • Janak de Zoysa
    • 7
  • Lisa K. Stamp
    • 8
  • Nicola Dalbeth
    • 2
  • Jennie Harré Hindmarsh
    • 9
  • Nuku Rapana
    • 10
  • Ranjan Deka
    • 11
  • Winston W. H. Eng
    • 12
  • Daniel E. Weeks
    • 12
    • 13
  • Ryan L. Minster
    • 13
  • Stephen T. McGarvey
    • 14
  • Satupa’itea Viali
    • 15
  • Take Naseri
    • 16
  • Muagututi’a Sefuiva Reupena
    • 17
  • Phillip Wilcox
    • 18
  • David Grattan
    • 4
    • 19
  • Peter R. Shepherd
    • 2
    • 4
  • Andrew N. Shelling
    • 1
  • Rinki Murphy
    • 2
    • 4
  • Tony R. Merriman
    • 3
    • 4
  1. 1.Department of Obstetrics and GynaecologyUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Medicine, Faculty of Medical and Health SciencesUniversity of Auckland University of AucklandAucklandNew Zealand
  3. 3.Department of BiochemistryUniversity of OtagoDunedinNew Zealand
  4. 4.Maurice Wilkins Centre for Molecular BiodiscoveryAucklandNew Zealand
  5. 5.Department of Anatomy and Medical ImagingUniversity of AucklandAucklandNew Zealand
  6. 6.Department of Paediatrics, Child and Youth HealthUniversity of AucklandAucklandNew Zealand
  7. 7.Renal ServicesWaitemata District Health BoardAucklandNew Zealand
  8. 8.Department of MedicineUniversity of Otago ChristchurchChristchurchNew Zealand
  9. 9.Ngāti Porou Hauora Charitable Trust, Te Puia SpringsTairāwhiti East CoastNew Zealand
  10. 10.Pukapuka Community of New Zealand Inc.AucklandNew Zealand
  11. 11.Department of Environmental HealthUniversity of Cincinnati College of MedicineCincinnatiUSA
  12. 12.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  13. 13.Department of Human Genetics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  14. 14.International Health Institute, Department of Epidemiology, Brown University School of Public Health, and Department of AnthropologyBrown UniversityProvidenceUSA
  15. 15.Samoa National Health ServiceApiaSamoa
  16. 16.Ministry of Health, Government of SamoaApiaSamoa
  17. 17.Bureau of Statistics, Government of SamoaApiaSamoa
  18. 18.Department of Mathematics and StatisticsUniversity of OtagoDunedinNew Zealand
  19. 19.Department of AnatomyUniversity of OtagoDunedinNew Zealand

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