The Pacific-specific CREBRF rs373863828 allele protects against gestational diabetes mellitus in Māori and Pacific women with obesity

Academic Article

Abstract

  • Aims/hypothesis: The CREBRF rs373863828 minor (A) allele is associated with increased BMI but reduced prevalence of type 2 diabetes in Māori and Pacific people. Given the shared aetiology of type 2 diabetes and gestational diabetes mellitus (GDM), we tested for an association between the CREBRF rs373863828 variant and GDM. Methods: We conducted a prospective cohort study of Māori and Pacific women nested within a nutritional intervention study for pregnant women with obesity. Women were enrolled at 12–17 weeks’ gestation and underwent anthropometry and collection of buffy coats for later genetic testing. GDM was diagnosed by 75 g OGTT at 24–28 weeks’ gestation using the International Association of Diabetes and Pregnancy Study Groups criteria. Genotyping was performed by real-time PCR with a custom CREBRF rs373863828 probe-set. The association between CREBRF rs373863828 and GDM was analysed separately by ethnic group using logistic regression, with effect estimates combined in a meta-analysis. Results: Of 112 Māori and Pacific pregnant women with obesity, 31 (28%) carried the CREBRF rs373863828 A allele (A/G or A/A) and 35 (31%) developed GDM. Women who carried the CREBRF rs373863828 A allele did not differ in BMI when compared with non-carriers (G/G). There was a fivefold reduction in the likelihood of GDM per CREBRF rs373863828 A allele (OR 0.19 [95% CI 0.05, 0.69], p = 0.01), independent of age, BMI and family history of diabetes (adjusted OR 0.13 [95% CI 0.03, 0.53], p = 0.004). GDM was diagnosed in 10% and 40% of women with and without the CREBRF rs373863828 A allele, respectively (no woman with the A/A genotype developed GDM). Conclusions/interpretation: The CREBRF rs373863828 (A) allele is associated with reduced likelihood of GDM in Māori and Pacific women with obesity and may improve GDM risk prediction. [Figure not available: see fulltext.]
  • Authors

    Published In

  • Diabetologia  Journal
  • Digital Object Identifier (doi)

    Author List

  • Krishnan M; Murphy R; Okesene-Gafa KAM; Ji M; Thompson JMD; Taylor RS; Merriman TR; McCowan LME; McKinlay CJD
  • Start Page

  • 2169
  • End Page

  • 2176
  • Volume

  • 63
  • Issue

  • 10