Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Wu, Ling; Cui, Long; Tam, Wing Hung; Ma, Rong; Wang, Chi Chiu

doi:10.1038/srep30539

Cited by 109 publications

(109 citation statements)

References 47 publications

(56 reference statements)

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“…However the literature suggests to use the adjusted data by age and BMI as these are often neglected confounders and concludes that this approach results in a more accurate analysis compared to the direct use of unadjusted raw data [18]. Therefore—after exclusion of the causative chain for our most significant findings—we indicate these genetic association results adjusted by age and BMI.…”

Section: Methodsmentioning

confidence: 85%

“…We conducted a case-control genetic association study in a Caucasian population with 77 gene variants that were either earlier reported to be associated with the GDM or with T2D due to that GDM and T2D share similar genetic susceptibility background [18]. In addition a few other gene variants (SNPs) with potential contribution to an important metabolic condition were also assessed to detect associations with GDM or other related traits.…”

Section: Discussionmentioning

confidence: 99%

“…Authors found that only in studies which included subjects with mean pre-pregnancy BMI higher than 25 kg/m 2 , but not with lower mean pre-pregnancy BMI values the MTNR1B rs10830963 risk variant was significantly associated with GDM [18]. Furthermore, in a recent study with early intervention (diet, lifestyle intervention from the 13 th gw) applied in high GDM risk individuals (BMI>30kg/m 2 ) only non-carriers of the risk allele G benefited from the 3 months intervention assessed by PG values at routine OGTT suggesting that MTNR1B rs10830963 variant could modify the efficacy of lifestyle interventions [35].…”

Section: Discussionmentioning

confidence: 99%

“…This might be due to differences in the study populations (ethnicity), small sample size and the different diagnostic criteria used. Most of the GWAS studies in this disease were conducted in Asian populations [11], highlighting the need for confirmation in Caucasian populations [18]. …”

Section: Introductionmentioning

confidence: 99%

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Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

et al. 2017

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ContextGenetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM).ObjectiveWe assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy.Methods960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values.ResultsThe most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT.ConclusionsWe confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria.

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Section: Methodsmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

et al. 2017

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“…However, these candidate genes only explain a small proportion of the heritability, and environmental influence is obviously important in the pathogenesis. The evidence for a genetic predisposition for GDM is not as robust as that for T2DM (5), but several systematic reviews and meta-analyses have highlighted genes such as Transcription Factor 7 Like 2 (TCF7L2), Melatonin receptor 1B (MTNR1B) and Insulin receptor substrate 1 (IRS1) among others to be important (21,22,23,24,25,26). Epigenetic modifications during pregnancy could be an interesting method to study the environmental influence (27), as several studies have reported the effect of GDM on birth outcomes and indicated that epigenetic alterations may be an important mediator (28).…”

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Epigenetic modifications and gestational diabetes: a systematic review of published literature

Moen

Sommer

Prasad

et al. 2017

European Journal of Endocrinology

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Objective: To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research. Design: Systematic review. Methods: We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016. Results: We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring. Conclusion: The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.

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Screening for monogenic subtypes of gestational diabetes in a high prevalence island population – A whole exome sequencing study

Pace

Vella

Craus

et al. 2021

Diabetes Metabolism Res

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Aims The reported frequency of monogenic defects of beta cell function in gestational diabetes (GDM) varies extensively. This study aimed to evaluate the frequency and molecular spectrum of variants in genes associated with monogenic/atypical diabetes in non‐obese females of Maltese ethnicity with GDM. Methods 50 non‐obese females who met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosis of GDM and with a first‐degree relative with non‐autoimmune diabetes were included in this study. Whole exome capture and high throughput sequencing was carried out. Rare sequence variants were filtered, annotated, and prioritised according to the American College for Medical Genetics guidelines. For selected missense variants we explored effects on protein stability and structure through in‐silico tools. Results We identified three pathogenic variants in GCK, ABCC8 and HNF1A and several variants of uncertain significance in the cohort. Genotype‐phenotype correlations and post‐pregnancy follow‐up data are described. Conclusions This study provides the first insight into an underlying monogenic aetiology in non‐obese females with GDM from an island population having a high prevalence of diabetes. It suggests that monogenic variants constitute an underestimated cause of diabetes detected in pregnancy, and that careful evaluation of GDM probands to identify monogenic disease subtypes is indicated.

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Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Cited by 109 publications

References 47 publications

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

MECHANISMS IN ENDOCRINOLOGY: Epigenetic modifications and gestational diabetes: a systematic review of published literature

Screening for monogenic subtypes of gestational diabetes in a high prevalence island population – A whole exome sequencing study

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