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Objective: To study the association of genes involved in the mitochondrial respiratory chain (MRC) pathway with body mass index (BMI) and obesity risk., Design: This work studies three cross-sectional populations from Spain, representing three provinces: HORTEGA (Valladolid, Northwest/Centre), SEGOVIA (Segovia, Northwest/centre) and PIZARRA (Malaga,South)., Setting: Forty-eight single nucleotide polymorphisms (SNPs) from MRC genes were selected and genotyped by SNPlex method. Association studies with BMI and obesity risk were performed for each population. These associations were then verified by analysis of the studied population as a whole (3731 samples)., Participants: A total of 3731 Caucasian individuals: 1502 samples from HORTEGA, 988 from PIZARRA and 1241 from SEGOVIA., Results: rs4600063 ( SDHC ), rs11205591 ( NDUFS5 ) and rs10891319 ( SDHD ) SNPs were associated with BMI and obesity risk (p values for BMI were 0.04, 0.0011 and 0.0004, respectively, and for obesity risk, 0.0072, 0.039 and 0.0038). However, associations between rs4600063 and BMI and between these three SNPs and obesity risk are not significant if Bonferroni correction is considered. In addition, rs11205591 and rs10891319 polymorphisms showed an additive interaction with BMI and obesity risk., Conclusions: Several polymorphisms from genes coding MRC proteins may be involved in BMI variability and could be related to the risk to become obese in the Spanish general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The interaction of selenium, a component of antioxidant selenoproteins, with genetic variation in lipid-related pathways has not been evaluated earlier as a potential determinant of blood lipid levels. We aimed at evaluating the effects of gene-environment interactions between plasma levels of selenium and polymorphisms in lipid metabolic pathways on plasma lipid levels in a study population from Spain (N=1,315). We observed statistically significant associations between plasma selenium and lipid levels (differences in total, low-density lipoprotein [LDL]-cholesterol, and triglycerides comparing the 80th with the 20th percentiles of plasma selenium levels were, respectively, 12.0 (95% confidence interval 6.3, 17.8), 8.9 (3.7, 14.2), and 9.0 (2.9, 15.2) mg/dl). We also found statistically significant interactions at the Bonferroni-corrected significance level (p=0.0008) between selenium and rs2290201 in FABP4 for total and LDL cholesterol levels and rs1800774 in CETP for elevated LDL cholesterol. Other polymorphisms showed statistically significant differential associations of plasma selenium levels and lipids biomarkers at the nominal p-value of 0.05. Reported statistical interactions with genes involved in lipid transport and transfer provide biological support to the positive associations of selenium with lipids shown in cross-sectional studies and lead to the hypothesis that selenium and lipid levels share common biological pathways that need to be elucidated in mechanistic studies.

Background/objectives: Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity., Subjects/methods: We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex., Results: We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53)., Conclusions: Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.

Scope: The serum fatty acid (FA) composition is influenced by dietary fat and the endogenous production of FAs. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme catalyzing the synthesis of MUFAs from saturated FAs. Variations in SCD1 activity have been associated with obesity, diabetes, or inflammation. We evaluated the associations between genetic variation of the SCD1 gene, SCD1 activity, intake of oil, and obesity in a population-based prospective study in southern Spain., Methods and Results: We collected phenotypic, metabolic, nutritional, and genetic information. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by GC. A total of nine single nucleotide polymorphisms (SNPs) of the SCD1 gene were analyzed by SNPlex technology. We found a significant association between SCD1 genetic variation and enzyme activity in four of nine polymorphisms studied. An interaction between rs10883463 and olive oil intake on the [18:1/18:0] desaturase index was found (p = 0.009). We also showed that genetic variations in the SCD1 gene were associated with obesity., Conclusion: Our results show a relationship between genetic variation of the SCD1 gene, enzyme activity, and the risk of obesity, an association that is not independent of the type of oil consumed., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution., Design: We performed a cross-sectional study in 2367 individuals from two population-based studies from different regions of Spain. The Hortega Study included 1436 individuals (693 women) 21-85 years old, and the Pizarra Study included 931 individuals (584 women) 18-65 years old. We evaluated three polymorphisms of the UCP2 gene., Results: The TT genotype of the rs660339 polymorphism and the AA genotype of the rs659366 polymorphism of the UCP2 gene were significantly associated with higher waist circumference in the Hortega Study. Furthermore, subjects carrying both genotypes (TT+AA) also showed higher central adiposity compared with other genotypes. This association was also present in the Pizarra Study. Moreover, in the pooled population, we found a stronger association with waist circumference. Even, we found association with BMI. Furthermore, rs659366 polymorphism was associated with the risk of abdominal obesity (P= 0·04: OR = 1·3; CI = 1·01-1·67)., Conclusions: Polymorphisms of the UCP2 gene (rs660339 and rs659366) were associated with central obesity. This study shows association between the UCP2 gene and the susceptibility to obesity and body fat distribution in a south European population., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)