Single Nucleotide Polymorphisms in CDKAL1 Gene Are Associated with Risk of Gestational Diabetes Mellitus in Chinese Population

Abstract

Gestational diabetes mellitus (GDM) is a growing public health concern for many reasons, and its etiology remains unclear. Due to the similarity of its pathophysiology with type 2 diabetes (T2DM), we evaluated the relationship between published T2DM susceptibility genes and the risk of GDM. A total of 303 SNPs from genes including IRS1, IGF2BP2, CDKAL1, GCK, TCF7L2, KCNQ1, and KCNJ11 and the risk of GDM were examined in a nested case-control study with 321 GDM cases and 316 controls. The odds ratios (ORs) and their 95% confidence interval (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and GDM in additive, recessive, dominant, and codominant models adjusting for maternal age, maternal BMI, parity, and family history of diabetes. At the gene level, CDKAL1 was associated with GDM risk. SNPs in the CDKAL1 gene including rs4712527, rs7748720, rs9350276, and rs6938256 were associated with reduced GDM risk. However, SNPs including rs9295478, rs6935599, and rs7747752 were associated with elevated GDM risk. After adjusting for multiple comparisons, rs9295478 and rs6935599 were still significant across the additive, recessive, and codominant models; rs7748720 and rs6938256 were significant in dominant and codominant models; and rs4712527 was only significant in the codominant model. Our study provides evidence for an association between the CDKAL1 gene and risk of GDM. However, its role in the GDM pathogenesis still needs to be verified by further studies.

The CDKAL1 rs7747752-Bile Acids Interaction Increased Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

“…The rs7747752 under study was significantly associated with increased GDM risk. Similar to our findings, another study also found that Chinese women with the rs7747752 polymorphism were predisposed to a high risk of GDM ( 8 ). Previous studies have reported significant interaction effects of CDKAL1 with lifestyle interventions, SFAs, and vitamin D on GDM risk ( 14 , 17 , 33 ).…”

Defining Heterogeneity Among Women With Gestational Diabetes Mellitus

“…Thus far, most genetic investigations of GDM have highlighted variants that are already known to increase risk of T2D (40,41), underscoring the overlap in the genetic architecture of the two conditions. Most studies have investigated known T2D-associated loci using GDM case-control studies in populations of various ethnic backgrounds including European, African American, Chinese, and Hispanic (42)(43)(44)(45)(46). The T2D-associated loci that have been most robustly associated with GDM are IRS1, IGF2BP2, CDKAL1, GCK, TCF7L2, MTNR1B, KCNJ11, and KCNQ1 (40).…”

Gestational Diabetes Mellitus: A Harbinger of the Vicious Cycle of Diabetes

“…There is a strong association between common T2D risk gene polymorphisms and GDM [ 79 ]. Five of the most identified genes in GDM are: (1) Transcription factor 7-like 2 [TCFL7L2] [ 80 , 81 ]; (2) Melatonin receptor 1B [MTNR1B] [ 82 , 83 ]; (3) CDK5 regulatory subunit-associated protein 1-like 1 [CDKAL1] [ 84 , 85 ]; (4) Potassium voltage-gated channel, KQT-like subfamily, member 1 [KCNQ1] [ 86 , 87 ]; and (5) Insulin receptor substrate-1 [IRS1] [ 88 , 89 ]. The most recent and comprehensive searches in the genetic and epigenetic etiology of GDM have been reviewed elsewhere [ 90 , 91 ].…”