Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction

Popova, Polina; Klyushina, Alexandra; Vasilyeva, Lyudmila B.; Tkachuk, Aleksandra; Vasukova, Elena; Anopova, Anna D.; Pustozerov, Evgenii; Горелова, И. В.; Кравчук, Е. Н.; Li, O.; Pervunina, Tatiana; Kostareva, Anna; Grineva, Elena

doi:10.3389/fendo.2021.628582

Cited by 53 publications

(41 citation statements)

References 30 publications

(37 reference statements)

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“…MTNR1B polymorphisms also have associations with GDM in Filipino and Pacific Islander populations. rs10830963 has been reported to have a strong correlation in a meta-analysis of GDM GWAS studies [ 65 ], and this finding has been seen among Korean, Greek [ 66 ], Russian [ 67 ] and Chinese women [ 42 ]. MTNR1A and MTNR1B encode for melatonin receptors and high-risk allele carriers at rs10830963 also have higher expression of MTNR1B in pancreatic beta cells, which leads to impaired insulin secretion [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic risk factors associated with gestational diabetes in a multi-ethnic population

et al. 2021

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Aims Genome-wide association studies have shown an increased risk of type-2-diabetes (T2DM) in patients who carry single nucleotide polymorphisms in several genes. We investigated whether the same gene loci confer a risk for gestational diabetes mellitus (GDM) in women from Hawaii, and in particular, Pacific Islander and Filipino populations. Methods Blood was collected from 291 women with GDM and 734 matched non-diabetic controls (Pacific Islanders: 71 GDM, 197 non-diabetic controls; Filipinos: 162 GDM, 395 controls; Japanese: 58 GDM, 142 controls). Maternal DNA was used to genotype and show allele frequencies of 25 different SNPs mapped to 18 different loci. Results After adjusting for age, BMI, parity and gravidity by multivariable logistic regression, several SNPs showed significant associations with GDM and were ethnicity specific. In particular, SNPs rs1113132 (EXT2), rs1111875 (HHEX), rs2237892 (KCNQ1), rs2237895 (KCNQ1), rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM in Filipinos. For Japanese, SNPs rs4402960 (IGFBP2) and rs2237892 (KCNQ1) were significantly associated with GDM. For Pacific Islanders, SNPs rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM. Individually, none of the SNPs showed a consistent association with GDM across all three investigated ethnicities. Conclusion Several SNPs associated with T2DM are found to confer increased risk for GDM in a multiethnic cohort in Hawaii.

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Section: Discussionmentioning

confidence: 99%

Genetic risk factors associated with gestational diabetes in a multi-ethnic population

et al. 2021

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“…In recent years, many genetic and non-genetic factors that may predispose women to GDM have been sought. Various genetic polymorphisms are being studied, as well as the expression of genes in human umbilical vein endothelial cells and in the placenta [4,5]. There are many similarities in the pathogenesis of GDM and Life 2021, 11, 806 2 of 10 type 2 diabetes [6]; therefore, genetic polymorphisms associated with type 2 diabetes are taken into account.…”

Section: Introductionmentioning

confidence: 99%

ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

Ustianowski

Malinowski

Kopytko

et al. 2021

Life

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Gestational diabetes mellitus (GDM) is carbohydrate intolerance that occurs during pregnancy. This disease may lead to various maternal and neonatal complications; therefore, early diagnosis is very important. Because of the similarity in pathogenesis of type 2 diabetes and GDM, the genetic variants associated with type 2 diabetes are commonly investigated in GDM. The aim of the present study was to examine the associations between the polymorphisms in the ADCY5 (rs11708067, rs2877716), CAPN10 (rs2975760, rs3792267), and JAZF1 (rs864745) genes and GDM as well as to determine the expression of these genes in the placenta. This study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation, according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. There were no statistically significant differences in the distribution of the ADCY5 gene (rs11708067, rs2877716) and CAPN10 gene (rs2975760, rs3792267) polymorphisms between pregnant women with normal carbohydrate tolerance and pregnant women with GDM. We have shown a lower frequency of JAZF1 gene rs864745 C allele carriers among women with GDM CC + CT vs. TT (OR = 0.60, 95% CI = 0.41–0.87, p = 0.006), and C vs. T (OR = 0.75, 95% CI = 0.60–0.95, p = 0.014). In addition, ADCY5 and JAZF1 gene expression was statistically significantly increased in the placentas of women with GDM compared with that of healthy women. The expression of the CAPN10 gene did not differ significantly between women with and without GDM. Our results indicate increased expression of JAZF1 and ADCY5 genes in the placentas of women with GDM as well as a protective effect of the C allele of the JAZF1 rs864745 gene polymorphism on the development of GDM in pregnant women.

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“…Therefore, their clinical benefit when applied to the most recent GDM definition has not yet been well investigated. Recently, a number of new markers have been evaluated for use in predicting GDM with variable success, such as protein biomarkers (23), adiponectin (24) and leptin (25), pentraxin 3 (26), trace elements (27), RNA (28), singlenucleotide polymorphisms (29), and other combined metabolite models (30)(31)(32)(33). The AUC values of some of these models can reach above 0.8.…”

Section: Discussionmentioning

confidence: 99%

Putrescine as a Novel Biomarker of Maternal Serum in First Trimester for the Prediction of Gestational Diabetes Mellitus: A Nested Case-Control Study

et al. 2021

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AimsEarly identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no acknowledged biomarker has proven clinically useful for the accurate prediction of GDM. In this study, we tested whether serum putrescine level changed in the first trimester and could improve the prediction of GDM.MethodsThis study is a nested case-control study conducted in Beijing Obstetrics and Gynecology Hospital. We examined serum putrescine at 8-12 weeks pregnancy in 47 women with GDM and 47 age- and body mass index (BMI)-matched normoglycaemic women. Anthropometric, clinical and laboratory variables were obtained during the same period. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of the prediction models.ResultsSerum putrescine in the first trimester was significantly higher in women who later developed GDM. When using putrescine alone to predict the risk of GDM, the AUC of the nomogram was 0.904 (sensitivity of 100% and specificity of 83%, 95% CI=0.832–0.976, P<0.001). When combined with traditional risk factors (prepregnant BMI and fasting blood glucose), the AUC was 0.951 (sensitivity of 89.4% and specificity of 91.5%, 95% CI=0.906-0.995, P<0.001).ConclusionThis study revealed that GDM women had an elevated level of serum putrescine in the first trimester. Circulating putrescine may serve as a valuable predictive biomarker for GDM.

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Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction

Cited by 53 publications

References 30 publications

Genetic risk factors associated with gestational diabetes in a multi-ethnic population

Genetic risk factors associated with gestational diabetes in a multi-ethnic population

ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

Putrescine as a Novel Biomarker of Maternal Serum in First Trimester for the Prediction of Gestational Diabetes Mellitus: A Nested Case-Control Study

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