In current meta- study, we found that the
IRS1 rs1801278 (C/T) were not significant associated with GDM risk under the dominant and allele models, but the
IRS1 rs1801278 (C/T) were significant associated with GDM risk under the recessive models. Several studies [
12‐
16] were performed to investigate the relationship between rs1801278 and GDM susceptibility, however these studies concluded inconsistent results. A case- control [
12] study performed in Saudi women suggested that the IRS-1 rs1801278 variant may associated with increased risk of GDM under the dominant model. A study [
13] for Greek population suggests that the risk of developing GDM is higher among female carriers of the minor allele within IRS1 gene rs1801278. But Shaat et al. [
14] concluded inconsistent results, they found a negative result on relationship between IRS1 gene rs1801278 and GDM risk. Although, three meta- studies [
17‐
19] have focused on this topic, and the three meta- analyses indicated that rs1801278 was associated with higher GDM risk, but in recent years, there have been new case-control studies [
20‐
22] have been performed, and these new studies concluded inconsistent result with previous meta- analysis. Wu et al. [
19] conducted a meta study suggested that GDM was associated with rs1801278(IRS1), but this relationship was not significant in Asian populations. In addition, the IRS1- rs1801278 was significantly affected by OGTT protocol and genotyping methods. Zhang et al. [
17] indicated that the minor alleles of IRS1- rs1801278 (Gly972Arg) were significantly associated with a higher risk of GDM, and another meta- study concluded similar results. From then on, additional case- control studies were performed. Popova et al. [
20] suggested that the distribution of genotype frequencies was not significant different between cases and controls. In 2021, Popova et al. [
21] conducted another case- control study in Russian women and they obtained similar results. Wu et al. [
22] performed a case- control study in Chinese females and found that there was no statistically significant difference in genotype frequency between the case and the control group.
Previous research [
30,
31] suggests that IRS1 is a substrate of insulin receptor tyrosine kinase and plays a crucial role in insulin signaling pathways. IRS1 protein can be expressed in many insulins sensitive tissues, and its tyrosine phosphorylation can trigger activation of phosphatidylinositol 3-kinase (PI3K) and translocation of glucose transporter [
32]. Evidence [
14] have shown that the IRS1 G972R polymorphism reduces insulin content in isolated human islets and impairs insulin secretion function.
Several limitations existed in this meta-analysis. Firstly, we could not analyze the data grouped by ethnic, because just two studies were conducted in Asian. Secondly, the pathogenesis of GDM is very complex, including genetic factors, environmental factors and the synergistic effects. Therefore, this study only analyzes the association between a single SNP and GDM, without involving gene- environmental synergistic effects.