CDKAL1 gene rs7756992 A/G and rs7754840 G/C polymorphisms are associated with gestational diabetes mellitus in a sample of Bangladeshi population: implication for future T2DM prophylaxis

Abstract

Background Association of single nucleotide polymorphisms (SNP) rs7756992 A/G and rs7754840 G/C of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene with the susceptibility of gestational diabetes mellitus (GDM) has been studied in a group of Bangladeshi women. Methods In this case–control study, 212 GDM patients and 256 control subjects were genotyped for rs7756992 and rs7754840 by PCR-RFLP and TaqMan™ allelic discrimination assay method respectively. Genotyping results were confirmed by DNA sequencing and replicated TaqMan™ assay. The odds ratios and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and GDM. Results The genotype frequencies of rs7756992-AA/AG/GG in the GDM group and the control group were 37%/48%, 53%/45%, 10%/7% and those of rs7754840-CC/CG/GG were 51%/55%, 40.1%/39.8%, 9%/5% respectively. Under dominant and log additive models rs7756992 was revealed significantly associated with GDM after being adjusted for family history of diabetes (FHD) and gravidity. Conversely, rs7754840 was significantly associated (P = 0.047) with GDM only under the recessive model after the same adjustment. The risk allele frequency of both SNPs was higher in the GDM group but significantly (P = 0.029) increased prevalence was observed in the rs7756992 G allele. When positive FHD and risk alleles of these SNPs were synergistically present in any pregnant woman, the chance of developing GDM was augmented by many folds. The codominant model revealed 2.5 and 2.1 folds increase in odds by AG (rs7756992) and GC (rs7754840) genotypes and 3.7 and 4.5 folds by GG (rs7756992) and CC (rs7754840) genotypes respectively. A significant 2.7 folds (P = 0.038) increase in odds of GDM resulted from the interaction of rs7756992 and family history of diabetes under the dominant model. The cumulative effect of multigravidity and risk alleles of these SNPs increased the odds of GDM more than 1.5 folds in different genotypes. Conclusion This study not only revealed a significant association between rs7756992 and rs7754840 with GDM but also provided the possibility as potential markers for foretelling about GDM and type 2 diabetes mellitus in Bangladeshi women.

Association of theCDKAL1gene polymorphism with gestational diabetes mellitus in Chinese women

“…The correlation between CDKAL1 gene rs7754840 and GDM risk has been explored in many studies, but the results varied considerably among different populations. Consistent with our conclusions, studies in South Korea, Malaysia, southern India and Bangladesh 18 20 36 37 showed a strong correlation between rs7754840 and the risk of GDM. Furthermore, a meta-analysis of Asian populations showed that the C allele of rs7754840 was significantly associated with the increased risk of GDM.…”

“… 41 42 However, another meta-analysis indicated a consistently strong relationship between rs7756992 with GDM risk in Asian and Caucasian populations. 26 Amin et al 18 also confirmed that the AG and GG genotypes of CDKAL1 rs7756992 increased the odds of GDM by 2.5-fold and 3.7-fold, respectively, in Bangladeshi population. This inconsistency may be due to differences in race, sample size and diagnostic criteria for GDM.…”

“… 20 21 However, the association between CDKAL1 gene polymorphisms and GDM risk has been less studied, and the results are highly controversial. 18 22–26 Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among individuals, which may change the encoded amino acids or influence gene expression and produce disease. 27 As far as we know, there are no studies involving CKDAL1 rs4712523 and rs4712524 in the Chinese GDM population, and the results of studies between other SNPs of CDKAL1 and GDM susceptibility have not been clarified.…”

Lost pigs of Angola: Whole genome sequencing reveals unique regions of selection with emphasis on metabolism and feed efficiency

“…Previous studies have shown that CDKAL1 gene overlaps with identified QTLs associated with cholesterol metabolism, homeostasis, transport and regulation in humans ( Cheon et al, 2018 ) and pigs ( Bovo et al, 2019 ). Polymorphisms in the CDKAL1 gene are reported to be associated with type 2 diabetes mellitus in several human populations ( Hu et al, 2009 ; Han et al, 2010 ; Naser et al, 2021 ; Amin et al, 2022 ; Ghosh et al, 2022 ), and the CDKAL1 gene is involved in the metabolism of insulin that affects glucose mediated mechanisms, crucial for feed-efficiency and other growth and adaptation traits ( Santos et al, 2020 ).…”

Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus

“…In European populations, CDKAL1 polymorphisms, i.e., rs7754840 and rs10946398, were not associated with the risk of GDM [ 15 , 16 ]. On the other hand, CDKAL1 polymorphisms were strongly associated with risk of GDM in Chinese and other Asian populations [ 17 , 18 ]. Single nucleotide polymorphism (SNP) rs7747752 is in the intron of CDKAL1 .…”