FTO and ADRB2 Genetic Polymorphisms Are Risk Factors for Earlier Excessive Gestational Weight Gain in Pregnant Women with Pregestational Diabetes Mellitus: Results of a Randomized Nutrigenetic Trial.

Karina Dos Santos,Verônica Marques Zembrzuski,Eliane Lopes Rosado,Ana Carolina Proença Da Fonseca,Marcelo Ribeiro-Alves,J Alfredo Martínez,Cláudia Saunders,Letícia Barbosa Gabriel Da Silva,Gabriella Pinto Belfort

doi:10.3390/nu14051050

Abstract

Excessive gestational weight gain (GWG) is associated with increased risk of maternal and neonatal complications. We investigated obesity-related polymorphisms in the FTO gene (rs9939609, rs17817449) and ADRB2 (rs1042713, rs1042714) as candidate risk factors concerning excessive GWG in pregnant women with pregestational diabetes. This nutrigenetic trial, conducted in Brazil, randomly assigned 70 pregnant women to one of the groups: traditional diet (n = 41) or DASH diet (n = 29). Excessive GWG was the total weight gain above the upper limit of the recommendation, according to the Institute of Medicine guidelines. Genotyping was performed using real-time PCR. Time-to-event analysis was performed to investigate risk factors for progression to excessive GWG. Regardless the type of diet, AT carriers of rs9939609 (FTO) and AA carriers of rs1042713 (ADRB2) had higher risk of earlier exceeding GWG compared to TT (aHR 2.44; CI 95% 1.03–5.78; p = 0.04) and GG (aHR 3.91; CI 95% 1.12–13.70; p = 0.03) genotypes, respectively, as the AG carriers for FTO haplotype rs9939609:rs17817449 compared to TT carriers (aHR 1.79; CI 95% 1.04–3.06; p = 0.02).

Highlights

Excessive gestational weight gain (GWG) affects half of pregnancies worldwide [1]and nearly 40% of pregnancies in Brazil [2]
In a sample of 70 Brazilian pregnant women with pregestational diabetes mellitus (DM), we found that the A allele carriers for rs9939609 (FTO gene) and rs1042713 (ADRB2 gene) had more than twice the risk of earlier exceeding GWG compared to TT and GG genotypes, respectively
We investigated obesity-related polymorphisms in fat mass and obesity-associated (FTO) and adrenoceptor beta 2 (ADRB2) genes as candidate genetic risk factors for excessive GWG in pregnant women with pregestational DM using traditional or Dietary Approach to Stop Hypertension (DASH) diets

Summary

Introduction

Excessive gestational weight gain (GWG) affects half of pregnancies worldwide [1]and nearly 40% of pregnancies in Brazil [2]. Excessive gestational weight gain (GWG) affects half of pregnancies worldwide [1]. In addition to increasing the immediate risk of perinatal complications, excessive GWG is associated with short- and long-term metabolic consequences for mothers and children and probably plays a key role in the metabolic programming of chronic diseases in the offspring [5]. The GWG recommendations [6,7] are based on the pre-pregnancy body mass index (BMI), but genetics, dietetics, and environmental factors appear to be involved in significant interindividual variation in weight gain during pregnancy [8,9]. FTO encodes a protein with demethylase function and is highly expressed in the hypothalamus, in the arcuate nucleus, suggesting that this gene plays an essential role in energy balance and body weight control [10]

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