胎儿FTO基因变异与孕期母体负荷后血糖水平的关联

Association of fetal FTO gene variants with maternal postload glucose levels in pregnancy.

作者信息

Firneisz Gábor, Nádasdi Ákos, Nemes Botond A, Németh László, Rosta Klara, Harreiter Jürgen, Kautzky-Willer Alexandra, Somogyi Anikó, Benyó Zoltán

机构信息

Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.

Healthware Consulting Ltd., Budapest, Hungary.

出版信息

Int J Obes (Lond). 2025 Aug 28. doi: 10.1038/s41366-025-01896-1.

DOI:10.1038/s41366-025-01896-1

PMID:40877565

Abstract

OBJECTIVE

The FTO rs9939609 variant is a major common genetic risk factor of adult obesity. We hypothesized that the rs9939609 variant of the fetus alters the plasma glucose (PG) levels during oral glucose tolerance test (OGTT) routinely performed between the 24-28th gestational week.

METHODS

We analysed the data of mother-neonate pairs from our prior gestational diabetes mellitus (GDM) case-control study (Hungarian-Austrian set, n = 858) and the HAPO study European ancestry subset (HAPO-EUR, n = 1374) using pre-pregnancy body mass index (BMI) and maternal age as covariates. The rs8050136 (complete LD with rs9939609) was used in the HAPO-EUR data set.

RESULTS

Fetal FTO variants were associated (dominant genetic model) with decreased maternal 60'min PG values (ß = -1.39 mmol/L, p = 1.9710; ß = -0.18 mmol/L, p = 4.3610; ß = -0.33 mmol/L, p = 2.1110) and with reduced incremental area under glucose curve at OGTT (ß =-1.70 mmolh/L, p = 3.8310; ß = -0.23 mmolh/L, p = 2.9110; ß = -0.39 mmolh/L, p = 1.61*10).

CONCLUSION

FTO risk variants carried by the fetus may indirectly influence maternal metabolism and could be associated with a flatter OGTT curve driven by the reduced 1 h postload PG levels in pregnancy.

摘要

目的

FTO基因rs9939609变异是成人肥胖的主要常见遗传风险因素。我们推测，胎儿的rs9939609变异会改变在妊娠24至28周期间常规进行的口服葡萄糖耐量试验（OGTT）中的血浆葡萄糖（PG）水平。

方法

我们使用孕前体重指数（BMI）和母亲年龄作为协变量，分析了我们之前的妊娠期糖尿病（GDM）病例对照研究（匈牙利 - 奥地利组，n = 858）以及HAPO研究欧洲血统亚组（HAPO - EUR，n = （此处原文有误，推测为1374））中母婴对的数据。在HAPO - EUR数据集中使用rs8050136（与rs9939609完全连锁不平衡）。

结果

胎儿FTO变异与母亲60分钟PG值降低（β = - 1.39 mmol/L，p = 1.97 * 10；β = - 0.18 mmol/L，p = 4.36 * 10；β = - 0.33 mmol/L，p = 2.11 * 10）以及OGTT时葡萄糖曲线下增量面积减少（β = - 1.70 mmolh/L，p = 3.83 * 10；β = - 0.23 mmolh/L，p = 2.91 * 10；β = - 0.39 mmol*h/L，p = 1.61 * 10）相关（显性遗传模型）。