常见的单核苷酸多态性与遗传风险评分相结合，为妊娠期糖尿病的病因学提供了新的见解。

Common single-nucleotide polymorphisms combined with a genetic risk score provide new insights regarding the etiology of gestational diabetes mellitus.

机构信息

The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to the Southern Medical University, Shanghai, China.

出版信息

Diabet Med. 2022 Aug;39(8):e14885. doi: 10.1111/dme.14885. Epub 2022 May 27.

DOI:10.1111/dme.14885

PMID:35587197

Abstract

AIMS

Few studies have constructed a genetic risk score (GRS) to predict the risk of gestaional diabetes mellitus (GDM). We tested the hypothesis that single-nucleotide polymorphisms (SNPs) confirmed for diabetes and obesity and the GRS are associated with GDM.

METHODS

We conducted a case-control study comprising 971 GDM cases and 1682 controls from the University of Hong Kong Shenzhen Hospital. A total of 1448 SNPs reported with type 2 diabetes (T2D), type 1 diabetes (T1D), and obesity were selected and the GRS based on SNPs associated with GDM was created.

RESULTS

We confirmed that rs10830963 (OR = 1.41,95% CI = 1.25, 1.59) in MTNR1B and rs2206734 (OR = 1.38, 95% CI = 1.22, 1.55) in CDKAL1 were strongly associated with the risk of GDM. Compared with participants with GRS based on T2D SNPs in the low tertile, the ORs of GDM across increasing GRS tertiles were 1.63 (95% CI 1.29, 2.06) and 2.72 (95% CI 2.18, 3.38) in the middle and high tertile, respectively. The positive associations between the GRS and the risk of GDM were also observed in GRS based on obesity/waist-to-hip ratio (WHR)/body mass index (BMI) SNPs. The resulting GRS for each allele increase was significantly associated with higher glycemic indices and lower HOMA-B values for GRS based on T2D SNPs, but not for GRS based on T1D SNPs and GRS based on obesity/WHR/BMI SNPs.

CONCLUSION

These findings indicate that GDM may share a common genetic background with T2D and obesity and that SNPs associated with insulin secretion defects have a vital role in the development of GDM.

摘要

目的

鲜有研究构建了用于预测妊娠期糖尿病（GDM）风险的遗传风险评分（GRS）。我们检验了以下假设，即已证实与糖尿病和肥胖相关的单核苷酸多态性（SNP）以及 GRS 与 GDM 相关。

方法

我们进行了一项病例对照研究，纳入了来自香港大学深圳医院的 971 例 GDM 病例和 1682 例对照。共选择了与 2 型糖尿病（T2D）、1 型糖尿病（T1D）和肥胖相关的 1448 个 SNP，并基于与 GDM 相关的 SNP 构建了 GRS。

结果

我们证实 MTNR1B 中的 rs10830963（OR=1.41，95%CI=1.25，1.59）和 CDKAL1 中的 rs2206734（OR=1.38，95%CI=1.22，1.55）与 GDM 风险密切相关。与 T2D SNP 低三分位组的参与者相比，GRS 三分位组中 GDM 的 OR 分别为 1.63（95%CI 1.29，2.06）和 2.72（95%CI 2.18，3.38）。在基于肥胖/腰臀比（WHR）/体重指数（BMI）SNP 的 GRS 中也观察到 GRS 与 GDM 风险之间的正相关。基于 T2D SNP 的 GRS 中每个等位基因增加的 GRS 与更高的血糖指数和更低的 HOMA-B 值显著相关，但基于 T1D SNP 的 GRS 和基于肥胖/WHR/BMI SNP 的 GRS 则没有。