Dataset Information

Association of the CDKAL1 gene polymorphism with gestational diabetes mellitus in Chinese women.

ABSTRACT:

Introduction

To identify the association of the cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene polymorphism with gestational diabetes mellitus (GDM) in the Chinese population.

Research design and methods

This case-control study enrolled 835 pregnant women with GDM and 870 pregnant women without diabetes who underwent antenatal examination during 24 to 28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Trained nurses collected their clinical information and blood samples. CDKAL1 gene rs10440833, rs10946398, rs4712523, rs4712524, rs7754840, rs7756992 and rs9465871 loci were genotyped by Agena MassARRAY system. SPSS V.26.0 software and online SHesis were used to analyze the relationship between CDKAL1 gene polymorphism and GDM susceptibility.

Results

After being adjusted for maternal age, prepregnancy body mass index (BMI), parity and family history of type 2 diabetes mellitus (T2DM), CDKAL1 gene rs10440833 (AA vs TT, OR=1.631, 95% CI 1.192 to 2.232), rs10946398 (CC vs AA, OR=1.400, 95% CI 1.028 to 1.905), rs4712523 (GG vs AA, OR=1.409, 95% CI 1.038 to 1.913), rs4712524 (GG vs AA, OR=1.418, 95% CI 1.043 to 1.929) and rs7754840 (CC vs GG, OR=1.407, 95% CI 1.036 to 1.911) polymorphisms were all associated with the increased risk of GDM. In addition, there was a powerful linkage disequilibrium (LD) among rs10946398, rs4712523, rs4712524 and rs7754840 (D'>0.900, r²>0.900). And there were significant differences in haplotype CGGC (OR=1.207, 95% CI 1.050 to 1.387) and AAAG (OR=0.829, 95% CI 0.721 o 0.952, p=0.008) between the GDM group and the control group.

Conclusions

rs10440833, rs10946398, rs4712523, rs4712524 and rs7754840 of CDKAL1 gene are associated with GDM susceptibility in central Chinese population.

SUBMITTER: Huang C

PROVIDER: S-EPMC10106001 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Association of the <i>CDKAL1</i> gene polymorphism with gestational diabetes mellitus in Chinese women.

Huang Chengjing C Guo Yan Y Li Wei W Xiang Bing B Zeng Jing J Zhou Feng F She Lu L Zhang Pei P Wang Shiwei S Liu Bei B Dai Qiong Q Yang Mei M

BMJ open diabetes research & care 20230401 2

<h4>Introduction</h4>To identify the association of the cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (<i>CDKAL1</i>) gene polymorphism with gestational diabetes mellitus (GDM) in the Chinese population.<h4>Research design and methods</h4>This case-control study enrolled 835 pregnant women with GDM and 870 pregnant women without diabetes who underwent antenatal examination during 24 to 28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province fro ...[more]

PMID: 37055162

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Project description:BackgroundDiabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations.AimWe aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations.MethodsWe examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); I 2 was used to assess the heterogeneity (if I 2 < 50%, the fixed-effects model was used; if I 2 ≥ 50%, the random-effects model was used for data consolidation); correlation was judged by a forest map; potential publication bias was tested by the Egger test (p > 0.05 indicates that there is no publication bias).ResultsFourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant (p < 0.01) for dominant genetic model (OR = 0.75, 95%CI = 0.64-0.88, p = 0.0003). But the allelic effect model (OR = 0.87, 95%CI = 0.75-1.02, p = 0.08) and the recessive genetic model (OR = 0.85, 95%CI = 0.66-1.10, p = 0.23) were not statistically significant (p > 0.01). In the non-Asian population, the differences were statistically significant (p < 0.01) for the allelic effect model (OR = 0.83, 95%CI = 0.77-0.88, p < 0.00001), the dominant model (OR = 0.79, 95%CI = 0.72-0.87, p < 0.00001), and the recessive model (OR = 0.78, 95%CI = 0.70-0.87, p < 0.0001).ConclusionIn this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations.

Project description:Background and purposeThe relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.MethodsSeveral databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.ResultsA total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.ConclusionThe MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.