Meta-Analysis of the Genetic Factors that Predisposed Asian Women to Gestational Diabetes Mellitus

Nurul Aishah Wan Noor ,Haizatul Husna Abdul Halim,Noor Fatihah Abu,Mohd Zaki Salleh ,Rabia’tul A’dawiyah Ariff Fadzilah ,Teh Lay Kek,Muhammad Hisyam Jamari,Muhamad Zafri Abdul Karim,Sharifah Nurdiyana Syed Mohd Bahktiar

doi:10.21315/mjps2021.19.2.9

Nurul Aishah Wan Noor , Haizatul Husna Abdul Halim + Show 7 more

Open Access

https://doi.org/10.21315/mjps2021.19.2.9

Copy DOI

Abstract

A meta-analysis was conducted to determine the significant risk alleles which increase the risks of gestational diabetes mellitus (GDM) in Asian to help in decision-making for genotyping of women at risk. PubMed, Science Direct and HuGE navigator were used to identify relevant studies from January 2000 to November 2018. Data extraction was done by five reviewers. Using Review Manager 5.3, association between 11 SNPs and risks of GDM was determined. Odds ratios (ORs) with 95% confidence intervals (95% CI), test of heterogeneity and publication bias were calculated. The result was considered significant if p-value ≤ 0.05. Twenty-one studies were identified based on the inclusion and exclusion criteria. From 11 genetic variants studied, 9 were found to have significant association with GDM susceptibility with different heterogeneity. Allelic, dominant and recessive genetic models show MTNR1B (rs138753, rs10830963) and CDKAL1 (rs7754840) are significantly associated with GDM. IGF2BP2 (rs4402960) was found to have significant association with GDM using allelic and recessive models. For TCF7L2 (rs7903146), significant association was found using allelic, dominant and over dominant models. KCNQ1 (rs2237892) showed association with GDM in dominant model only. Strong associations with increased susceptibility for GDM were also found for GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (rs1695). However, MTNR1B (rs10830962) and PPARγ2 are lack of association with GDM risk in Asian population. Nine genetic variants were associated with increased GDM risk in Asian population. Screening of these polymorphisms to identify pregnant women at risk is recommended for prevention and personalised intervention.

Highlights

Gestational diabetes mellitus (GDM) is commonly known as hyperglycaemia during pregnancy
A meta-analysis was conducted to determine the significant risk alleles which increase the risks of gestational diabetes mellitus (GDM) in Asian to help in decision-making for genotyping of women at risk
The search strategy consisted of queries of multiple combination ‘gestational diabetes mellitus’, ‘GDM’ and ‘genetic polymorphisms’, with names of specific genes combined with the search term ‘gestational diabetes mellitus’

Summary

Introduction

Gestational diabetes mellitus (GDM) is commonly known as hyperglycaemia during pregnancy. Diagnosis of GDM mainly follows the guidelines by American Diabetes Association (ADA) or International Association of Diabetes and Pregnancy Study Groups (IADPSG), using oral glucose tolerance test (OGTT) at around 24–28 weeks of gestation or as early as possible in women with high risk of GDM. The risk factors for GDM include age ≥ 25 years old, body mass index (BMI) ≥ 27 kg/m2, first degree relative with diabetes mellitus (DM), history of macrosomia, bad obstetric history and persistent glycosuria. Some researchers suggested the use of other tests or parameters for the diagnosis and identification of risks for GDM, such as haemoglobin A1c (HbA1c), other biomarkers and genetic tests (Rodrigo and Glastras 2018). Rapid advances and cost reductions of sequencing technologies, coupled with the completion of Human Genome Project, had made possible to identify regions of the genome harbouring susceptibility genes (Watanabe et al 2007)

Methods

Results

Conclusion