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采用分层方法研究妊娠期糖尿病患者孕前肥胖相关神经内分泌紊乱候选基因中的遗传多态性。

Genetic polymorphisms in neuroendocrine disorder-related candidate genes associated with pre-pregnancy obesity in gestational diabetes mellitus patients by using a stratification approach.

作者信息

Lee Kai Wei, Ching Siew Mooi, Devaraj Navin Kumar, Hoo Fan Kee

机构信息

Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

出版信息

Ann Transl Med. 2020 Sep;8(17):1060. doi: 10.21037/atm-20-1579.

Abstract

BACKGROUND

Certain candidate genes have been associated with obesity. The goal of this study is to determine the association between thirteen neuroendocrine disorder-related candidate genes and pre-pregnancy obesity among gestational diabetes mellitus (GDM) patients using the stratification approach defined the Asian and International criteria-based body mass index (BMI).

METHODS

This was a post-hoc case-control exploratory sub-analysis of a cross-sectional study among GDM women to determine which candidate single nucleotide polymorphisms (SNPs) related to neuroendocrine disorders may be associated with obesity. Factors were adjusted for socio-demographic characteristics and concurrent medical problems in this particular population. Pre-pregnancy BMI and concurrent medical profiles were obtained from maternal health records. Obesity is defined as BMI of ≥27.5 kg/m for Asian criteria-based BMI and >30 kg/m for International criteria-based BMI. Thirteen candidate genes were genotyped using Agena MassARRAY and examined for association with pre-pregnancy obesity using multiple logistic regression analysis. The significant difference threshold was set at P value <0.05.

RESULTS

Three hundred and twelve GDM women were included in this study; 60.9% and 44.2% of GDM patients were obese using Asian and International criteria-based BMI, respectively. GDM patients with AA or AG genotypes in specific SNP of brain-derived neurotrophic factor () (G > A in rs6265) are more likely to be obese (adjusted odd ratio =2.209, 95% CI, 1.305, 3.739, P=0.003) compared to those who carry the GG genotype in the SNP adjusted for parity, underlying with asthma, heart disease, anaemia, education background in the International criteria-based BMI stratification group. On the other hand, there were no associations between other candidate genes (, , , , , , , , , , and ) and maternal obesity.

CONCLUSIONS

In summary, rs6265 is significantly associated with pre-pregnancy obesity among GDM patients. The exact role of adjusted for diet intake and lifestyle factors merits further investigation.

摘要

背景

某些候选基因与肥胖有关。本研究的目的是采用基于亚洲和国际标准的体重指数(BMI)分层方法,确定13个神经内分泌紊乱相关候选基因与妊娠期糖尿病(GDM)患者孕前肥胖之间的关联。

方法

这是一项对GDM女性进行的横断面研究的事后病例对照探索性亚分析,以确定哪些与神经内分泌紊乱相关的候选单核苷酸多态性(SNP)可能与肥胖有关。针对该特定人群的社会人口统计学特征和并发医疗问题对因素进行了调整。孕前BMI和并发医疗状况从产妇健康记录中获取。肥胖定义为基于亚洲标准的BMI≥27.5kg/m²,基于国际标准的BMI>30kg/m²。使用Agena MassARRAY对13个候选基因进行基因分型,并使用多元逻辑回归分析检查其与孕前肥胖的关联。显著差异阈值设定为P值<0.05。

结果

本研究纳入了312名GDM女性;分别采用基于亚洲和国际标准的BMI,60.9%和44.2%的GDM患者肥胖。在基于国际标准的BMI分层组中,经产次、潜在哮喘、心脏病、贫血、教育背景调整后,脑源性神经营养因子(BDNF)特定SNP(rs6265中G>A)具有AA或AG基因型的GDM患者比携带GG基因型的患者更易肥胖(调整后的优势比=2.209,95%CI,1.305,3.739,P=0.003)。另一方面,其他候选基因([基因名称逐一列出])与母亲肥胖之间无关联。

结论

总之,rs6265与GDM患者孕前肥胖显著相关。考虑饮食摄入和生活方式因素后BDNF的确切作用值得进一步研究。

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