Investigating the genetic factors for gestational diabetes mellitus (GDM) in a black South African cohort

Abstract

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance first diagnosed during pregnancy. Many adverse pregnancy outcomes and long-term health implications exist for mothers with GDM, as well as their offspring. There is evidence of a genetic contribution to the risk of developing GDM; single nucleotide polymorphisms (SNPs) in Maturity Onset Diabetes of the Young (MODY) genes, and genes shown to influence type 2 diabetes (T2D) susceptibility, attribute 4- 10% of GDM cases. This study focused on selected SNPs from five MODY genes and one T2D-associated gene, and aimed to investigate if these variants were associated with GDM in a black South African cohort. Genotyping was carried out for 23 SNPs in DNA samples from 80 GDM-positive and 160 GMD-negative women, and the correlations were statistically assessed using PLINK. Analysis revealed that, rs4581569, an intronic SNP in the Pancreatic and Duodenal Homeobox 1 (PDX1) gene was significantly associated with a decreased risk of GDM and low fasting glucose levels. Since rs4581569 tags one other SNP (rs9512918) in the gene region, and may be linked to other SNPs, the SNP might only be indirectly associated with GDM. The associated SNP is not specific to the South African population as the minor allele frequency was similar globally when compared to publicly available genetic variation data from the 1000 Genomes Project. The association found is a novel discovery and prompts further investigation to establish the significance of this SNP as a protective factor against GDM development.