Association of HHEX and SLC30A8 Gene Polymorphisms with Gestational Diabetes Mellitus Susceptibility: A Meta-analysis

Genetics plays a role in the development of gestational diabetes mellitus (GDM), which poses serious risks to pregnant women and their children. Several studies have demonstrated a link between GDM susceptibility and rs13266634 C/T polymorphism in SLC30A8 gene and rs1111875 C/T and rs5015480 C/T, which are located near the linkage disequilibrium block containing the IDE, HHEX, and KIF11 genes. However, the results are conflicting. Therefore, we aimed to investigate the association between susceptibility to GDM and HHEX and SLC30A8 gene polymorphisms. PubMed, Web of Science, EBSCO, CNKI, Wanfang Data, VIP, and SCOPUS were used to search for research articles. The quality of the selected literature was evaluated using the Newcastle-Ottawa scale. A meta-analysis was performed using Stata 15.1. Allelic, dominant, recessive, homozygote, and heterozygote models were used for the analysis. Nine articles with 15 studies were included. (1) Four studies about HHEX rs1111875 showed that the C allele was associated with the susceptibility to GDM; (2) three studies on HHEX rs5015480 indicated that the C allele in rs5015480 was significantly associated with GDM; (3) eight studies about SLC30A8 rs13266634 showed that the C allele was significantly associated with the susceptibility to GDM; and (4) a subgroup analysis showed that the rs5015480 polymorphism in HHEX and rs13266634 polymorphism in SLC30A8 gene were associated with GDM susceptibility in Asians. The meta-analysis provided evidence that the C allele in rs1111875 and rs5015480 in HHEX and rs13266634 in SLC30A8 can increase the risk of GDM.PROSPERO registration number CRD42022342280.