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Meoli L.,Center for Cardiovascular Research Charite | Isensee J.,Center for Cardiovascular Research Charite | Isensee J.,University of Cologne | Zazzu V.,Center for Cardiovascular Research Charite | And 11 more authors.
Gene | Year: 2014

The G protein-coupled receptor 30 (GPR30) has been claimed as an estrogen receptor. However, the literature reports controversial findings and the physiological function of GPR30 is not fully understood yet. Consistent with studies assigning a role of GPR30 in the cardiovascular and metabolic systems, GPR30 expression has been reported in small arterial vessels, pancreas and chief gastric cells of the stomach. Therefore, we hypothesized a role of GPR30 in the onset and progression of cardiovascular and metabolic diseases. In order to test our hypothesis, we investigated the effects of a high-fat diet on the metabolic and cardiovascular profiles of Gpr30-deficient mice (GPR30-lacZ mice). We found that GPR30-lacZ female, rather than male, mice had significant lower levels of HDL along with an increase in fat liver accumulation as compared to control mice. However, two indicators of cardiac performance assessed by echocardiography, ejection fraction and fractional shortening were both decreased in an age-dependent manner only in Gpr30-lacZ male mice. Collectively our results point to a potential role of Gpr30 in preserving lipid metabolism and cardiac function in a sex- and age-dependent fashion. © 2014 Elsevier B.V.

Tyrrell J.,University of Exeter | Richmond R.C.,University of Bristol | Richmond R.C.,Rotterdam University | Palmer T.M.,University of Warwick | And 89 more authors.
JAMA - Journal of the American Medical Association | Year: 2016

IMPORTANCE Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. OBJECTIVE To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. DESIGN, SETTING, AND PARTICIPANTS Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30 487 women in 18 studies were analyzed. Participants were of European ancestry from population-or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. EXPOSURES Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. MAIN OUTCOME AND MEASURE Offspring birthweight from 18 studies. RESULTS Among the 30 487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95%CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95%CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10-14) and -4 g (95%CI, -6 to -2g) per SBP-raising allele (P = 1×10-5), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95%CI, 17 to 93 g). A 1-SD ( ≈ 7.2mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95%CI, 80 to 147 g). However, a 1-SD ( ≈ 10mmHg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95%CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. CONCLUSIONS AND RELEVANCE In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes. Copyright 2016 American Medical Association. All rights reserved.

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