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Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus.

ABSTRACT: Introduction:Pre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women. Patients and methods:Women with GDM (n?=?160) and without GDM (n?=?145) were included in case-controlled study. Genotyping of the HNF1A gene (p.I27L rs1169288, p.98V rs1800574, p.S487N rs2464196), the VDR gene (p.BsmI rs1544410, p.ApaI rs7975232, p.TaqI rs731236, p.FokI rs2228570), and FTO gene (rs9939609) SNPs were performed by using RT-PCR. Results:The FTO AA genotype was associated with an increased risk of having GDM (AA vs. AT?+?TT, 24.4% vs. 12.4%, OR?=?2.27, 95% CI [1.23-4.19], p?=?0.007). The HNF1A p.I27L GT/TT genotype was associated with increased GDM risk (GT?+?TT vs. GG-wild, 79.4% vs. 65.5%, OR?=?2.02, 95% CI 1.21-3.38], p?=?0.007). However, all VDR gene SNPs and the HNF1A p.A98V, p.S487N were not associated with having GDM (p?>?0.05). The FTO AA genotype was associated with an increased risk for pre-pregnancy overweight/obesity (OR?=?1.43, 95% CI [1.25-3.4], p?=?0.035), but not associated with excessive GWG after adjusting for pre-pregnancy weight (p?>?0.05). Pre-pregnancy weight, weight at delivery, and GWG did not differ in both VDR and HNF1A gene carriers (p?>?0.05). HOMA-IR and HbA1c were increased in both p.I27L TT and FTO AA genotype carriers (p?

SUBMITTER: Beysel S

PROVIDER: S-EPMC6518700 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus.

Beysel Selvihan S Eyerci Nilnur N Ulubay Mustafa M Caliskan Mustafa M Kizilgul Muhammed M Hafızoğlu Merve M Cakal Erman E

Diabetology & metabolic syndrome 20190514

<h4>Introduction</h4>Pre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women.<h4>Patients and methods</h4>Women with GDM (n = 160) and without GDM (n = 145) were included in case-controlled stud ...[more]

PMID: 31114636

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Project description:Excessive pre-pregnancy weight is a known risk factor of pregnancy complications. The purpose of this analysis was to assess the relationship between several categories of maternal weight and the risk of developing hypertension and diabetes in pregnancy, and the relationship of these complications with the results of the newborn. It was carried out in a common cohort of pregnant women and taking into account the influence of disturbing factors. Our analysis was conducted in a prospective cohort of 912 Polish pregnant women, recruited during 2015-2016. We evaluated the women who subsequently developed diabetes with dietary modification (GDM-1) (n = 125) and with insulin therapy (GDM-2) (n = 21), as well as the women who developed gestational hypertension (GH) (n = 113) and preeclampsia (PE) (n = 24), compared to the healthy controls. Odds ratios of the complications (and confidence intervals (95%)) were calculated in the multivariate logistic regression. In the cohort, 10.8% of the women had pre-pregnancy obesity (body mass index (BMI) ? 30 kg/m2), and 36.8% had gestational weight gain (GWG) above the range of the Institute of Medicine recommendation. After correction for excessive GWG and other confounders, pre-pregnancy obesity (vs. normal BMI) was associated with a higher odds ratio of GH (AOR = 4.94; p < 0.001), PE (AOR = 8.61; p < 0.001), GDM-1 (AOR = 2.99; p < 0.001), and GDM-2 (AOR = 11.88; p <0.001). The threshold risk of development of GDM-2 occurred at lower BMI values (26.9 kg/m2), compared to GDM-1 (29.1 kg/m2). The threshold point for GH was 24.3 kg/m2, and for PE 23.1 kg/m2. For GWG above the range (vs. GWG in the range), the adjusted odds ratios of GH, PE, GDM-1, and GDM-2 were AOR = 1.71 (p = 0.045), AOR = 1.14 (p = 0.803), AOR = 0.74 (p = 0.245), and AOR = 0.76 (p = 0.672), respectively. The effect of maternal edema on all the results was negligible. In our cohort, hypertension and diabetes were associated with incorrect birth weight and gestational age at delivery. Conclusions: This study highlights the importance and influence of excessive pre-pregnancy maternal weight on the risk of pregnancy complications such as diabetes and hypertension which can impact fetal outcomes.

Project description:BackgroundClinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methodsA genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).ResultsApproximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.ConclusionsWe found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Project description:BackgroundGestational diabetes mellitus (GDM) is a common complication of pregnancy. It may predispose offspring to increased fat mass (FM) and the development of obesity, however few data from Latin America exist.ObjectiveTo investigate the influence of GDM on newborn FM in mother-newborn pairs recruited from a public maternity care center in São Paulo, Brazil.MethodsData were collected cross-sectionally in 2013-2014 from 72 mothers diagnosed with GDM, and 211 mothers with normal glucose tolerance (NGT). Newborn FM was evaluated by air-displacement plethysmography (PEA POD), and relevant demographic and obstetric data were collected from hospital records. Associations between maternal GDM status and newborn FM were investigated by multiple linear regression analysis, with adjustment for maternal age, pre-pregnancy BMI, gestational weight gain, type of delivery, sex of the child, and gestational age.ResultsFM was greater in GDM versus NGT newborns in a bivariable model (Median (IQR), GDM: 0.35 (0.3) kg vs. NGT: 0.27 (0.2) kg, p = 0.02), however GDM status was not a significant predictor of FM with adjustment for other variables. Rather, pre-pregnancy BMI (coefficient (?) 1.46; 95% confidence interval (CI) 0.66, 2.27), gestational weight gain (? 1.32; 95% CI 0.49, 2.15), and male sex (? -17.8; 95% CI -27.2, -8.29) predicted newborn FM. Analyzing GDM and NGT groups separately, pre-pregnancy BMI (? 6.75; 95% CI 2.36, 11.1) and gestational weight gain (? 5.64; 95% CI 1.16, 10.1) predicted FM in the GDM group, while male sex alone predicted FM in the NGT group (? -12.3; 95% CI -18.3, -6.34).ConclusionsCombined model results suggest that in our cohort, pre-pregnancy BMI and gestational weight gain are more important risk factors for increased neonatal FM than GDM. However, group-specific model results suggest that GDM status may contribute to variation in the relationship between maternal/offspring factors and FM. Our use of a binary GDM variable in the combined model may have precluded clearer results on this point. Prospective cohort studies including data on maternal pre-pregnancy BMI, GWG, and glycemic profile are needed to better understand associations among these variables and their relative influence on offspring FM.

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Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus.

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Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus.

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