Meta-analysis of HNF1A-MODY3 variants among human population.

Rachna Behl,Shalini Gupta,Modupe M Anthony,Abdulrahman Tudu Ibrahim,Xuanyu S Fang,Ikechukwu Okoye,Bhavya Saini,Arinola B Olaonipekun,Chinaza Nwanya,Ogunfile Foluso,Dibyendu Biswas,Shruti Poojary,Nishtha Malhotra,Sopuluchukwu Ugwu,Sanniya Middha,Vinay Joshi,Bhushan Wagh,Chukwuemelie Aginah

doi:10.1007/s40200-022-00975-8

Abstract

Previously, numerous case-control studies have highlighted variants responsible for Maturity onset diabetes of young (MODY). However, these studies have been conducted among diverse populations and hence yielded contradictory results. We, therefore, performed a meta-analysis to precisely find the association of SNPs with the disease for the HNF1A gene. Meta-analysis of clinically defined studies deciphering mutations in the HNF1A gene responsible for the development of MODY3 was conducted among various populations to determine associations using statistical approaches. The curation of 505 research articles published between the years 2000-2021 was carried out. Visualization of data-related protocols and statistical-analysis were conducted, which led to the identification of highly prevalent mutations among different populations (majorly Europe). Further comparison between the frequencies of the control (healthy population) and test (diseased population) dataset generated through curation was performed. We identified nine MODY3 mutations (rs587776825, rs1169288, rs1800574, rs2464196, rs137853244, rs137853238, rs587780357, rs137853240 and rs137853243) at the genome-wide significance level ( p < 5.0 × 10-8). The present study confirmed that the data does not follow a normal distribution. Further, the data was confirmed to be a more homogenous type with frequencies having a significant association with the disease. This meta-analysis found significant associations of mutations in HNF1A with MODY3, consistent with previous studies. Our findings should help elucidate the mutations in a compiled form responsible for causing MODY3. The online version contains supplementary material available at 10.1007/s40200-022-00975-8.

Highlights

Maturity onset diabetes of young (MODY) is a noninsulin-dependent diabetes mellitus (NIDDM) that follows an autosomal dominant inheritance pattern [1, 2]
We identified nine MODY3 mutations at the genome-wide significance level (p
Our findings should help elucidate the mutations in a compiled form responsible for causing MODY3

Summary

Introduction

MODY is a noninsulin-dependent diabetes mellitus (NIDDM) that follows an autosomal dominant inheritance pattern [1, 2]. It is challenging to interpret accurate incidence at the global level as MODY is often misdiagnosed as type 1 and type 2 diabetes mellitus [8] Since it is a rare disease, its incidence varies among different populations. Numerous case-control studies have highlighted variants responsible for Maturity onset diabetes of young (MODY) These studies have been conducted among diverse populations and yielded contradictory results. We performed a meta-analysis to precisely find the association of SNPs with the disease for the HNF1A gene

Methods

Results

Conclusion