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

Keke Wang,Yawei Zhang,Ying Wang,Yongliang Feng,Feng Zhao,Ping Zhang,Wenqiong Du,Hailan Yang,Suping Wang,Jamie Ko,Tianbi Han,Weiwei Wu,Qiong Chen,Feifei Yang

doi:10.1155/2019/3618103

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.

Highlights

Gestational diabetes mellitus (GDM) is a public health concern due to its large disease burden and its short- and long-term adverse health impact on pregnant women and their offspring including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) [1]
The CDKAL1 gene located in the short arm of human chromosome 6 could affect the function of β-cells through inhibiting the activity of CDK5 and acting as a tRNA-modifying enzyme [15], and risk alleles in this gene could affect the process of proinsulin conversion to insulin through protein translation
Results from a GWA study in Korean women suggested that rs7754840 in CDKAL1 is strongly associated with GDM [20], and subsequent meta-analysis confirmed that the C allele of rs7754840 was associated with elevated risk of GDM [6]

Summary

Introduction

Gestational diabetes mellitus (GDM) is a public health concern due to its large disease burden and its short- and long-term adverse health impact on pregnant women and their offspring including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) [1]. GDM shares common risk factors with T2DM, including family history of diabetes, obesity, high maternal age, Journal of Diabetes Research abnormal glucose tolerance, and specific ethnicity [4]. GDM has been suggested as precursor for T2DM by some researchers [5]. It is possible that the T2DM susceptibility genes were mostly found in GWA studies or metaanalysis normally with large sample size and weak effect, but those found in GDM studies often have small sample size resulting in insufficient statistical power to identify weak effects [7]

Methods

Results

Conclusion