Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
Department of Medicine, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Diabetologia. 2020 Oct;63(10):2169-2176. doi: 10.1007/s00125-020-05202-8. Epub 2020 Jul 12.
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.
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.
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. Graphical abstract.
目的/假设：CREBRF rs373863828 次要（A）等位基因与毛利人和太平洋岛民的 BMI 增加但 2 型糖尿病患病率降低有关。鉴于 2 型糖尿病和妊娠糖尿病（GDM）的发病机制相同，我们检测了 CREBRF rs373863828 变体与 GDM 之间的关联。
我们对嵌套在肥胖孕妇营养干预研究中的毛利人和太平洋岛妇女进行了前瞻性队列研究。妇女在 12-17 周妊娠时入组，并进行人体测量和收集用于以后进行基因检测的缓冲液。GDM 通过 24-28 周妊娠的 75g OGTT 根据国际糖尿病与妊娠研究组标准诊断。通过实时 PCR 用定制的 CREBRF rs373863828 探针集进行基因分型。使用逻辑回归分别按种族群体分析 CREBRF rs373863828 与 GDM 的关联，并用荟萃分析合并效应估计值。
在 112 名肥胖的毛利人和太平洋岛妇女中，有 31 名（28%）携带 CREBRF rs373863828 A 等位基因（A/G 或 A/A），35 名（31%）发生 GDM。与非携带者（G/G）相比，携带 CREBRF rs373863828 A 等位基因的妇女在 BMI 方面没有差异。每增加一个 CREBRF rs373863828 A 等位基因，GDM 的发生几率就会降低五倍（OR 0.19 [95%CI 0.05, 0.69]，p=0.01），独立于年龄、BMI 和糖尿病家族史（调整后的 OR 0.13 [95%CI 0.03, 0.53]，p=0.004）。分别有 10%和 40%的携带和不携带 CREBRF rs373863828 A 等位基因的妇女被诊断为 GDM（无携带 A/A 基因型的妇女发生 GDM）。
结论/解释：CREBRF rs373863828（A）等位基因与肥胖的毛利人和太平洋岛妇女的 GDM 发生几率降低相关，可能改善 GDM 风险预测。图形摘要。
