Influence of maternal educational level on the association between the rs3809508 neuromedin B gene polymorphism and the risk of obesity in the HELENA study

Abstract

Objective: Neuromedin B (NMB) is a bombesin-like peptide, which inhibits food intake and modulates stress-related behaviour. An NMB gene polymorphism (P73T) has been earlier associated with obesity and abnormal eating behaviour in adults. Methods: The association between four NMB polymorphisms and obesity-related phenotypes was investigated in the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (n ¼ 1144, 12-17-year-old European adolescents). This population was genotyped for the NMB rs1107179, rs17598561, rs3809508 and rs1051168 (P73T) polymorphisms. Obesity was defined according to Cole et al. (BMJ 2000; 320: 1240-1243 criteria; eating behaviour was assessed by the Eating Behaviour and Weight Problems Inventory for Children (EWI-C) and the food choices and preferences questionnaires. Familial socioeconomic status (SES) was assessed through the parents' educational level. Results: Only the genotype distribution of rs3809508 differed according to obesity status, as the TT genotype was more frequent in obese than in non-obese adolescents (8.6% vs 3.1%, P ¼ 0.05; adjusted odds ratio for obesity (95% confidence interval): 2.85 (1.11-7.31), P ¼ 0.03). Moreover, TT subjects had higher body mass index (22.8 ± 4.4 kg m -2 vs 21.3 ± 3.7 kg m -2 , P ¼ 0.02), waist circumference (75.8±9.7 cm vs 72.2±9.3 cm, P ¼ 0.006), waist-to-hip ratio (0.84±0.14 vs 0.79±0.07, Po0.0001) and waist-to-height ratio (0.47 ± 0.06 vs 0.44 ± 0.55, P ¼ 0.002) than C allele carriers. The effects of this single nucleotide polymorphism on all anthropometric values were influenced by the maternal SES, in that a low maternal educational level aggravated the phenotype of adolescents carrying the TT genotype (interactions: Po0.02). No association with EWI-C scores was found, although sweet craving was a more frequent cause of between-meal food intake in TT subjects than in C allele carriers (24.3% vs 9.2%, P ¼ 0.01). Conclusion: In European adolescents, the TT genotype of the NMB rs3809508 polymorphism was associated with a higher risk of obesity. Moreover, the effects of this polymorphism on anthropometric values were influenced by the maternal educational level.

Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population

“…The statistical significance of this interaction remains when the GP and OHP samples are included in a joint analysis. Although there is ample evidence that educational level is an important environmental variable associated with obesity and cardiovascular risk [1–7], there have been scarcely any studies that have examined the interaction of this variable with the effects of genetic variability in determining BMI [11–13], the exception being a recent publication by Holzapfel et al [34], that investigates the association between SNPs in the TMEM18 and FTO genes with educational level as well as income; however, the authors did not formally analyze the interaction between these SNPs and education in determining BMI and obesity, and we cannot compare our results with theirs [34]. …”

“…Thus, a study undertaken on Danish twins [12], investigated how genetic and environmental variance in physical health differed with level of education, and concluded that education reduced the influence of genetic susceptibility to poor health, suggesting that this might take place because more educated people manage their environments better to protect their health. Concerning the analysis of specific loci, there is one study showing that a low educational level aggravated the association between the rs3809508 neuromedin B single nucleotide polymorphism (SNP) and the risk of obesity in the HELENA study [13]. …”

Bombesin receptor subtype 3 as a potential target for obesity and diabetes

“…Two SNPs-rs1414839 y rs967790-in the gene encoding the NMBR have been associated with higher weight loss in patients undergoing Roux-en-Y gastric bypass surgery[118]. Furthermore, a rs3809508 polymorphism of the gene encoding the peptide NMB, as well as other mutations in the NMB gene, is associated with increased risk of obesity[119–121]. …”

Examining for an association between candidate gene polymorphisms in the metabolic syndrome components on excess weight and adiposity measures in youth: a cross-sectional study

“…Similarly, a variant of the APOA2 gene increases the association with obesity in those consuming high levels of saturated fatty acids [50]. Another study reported the influence of maternal education on the effect of a variant of the neuromedin B gene on obesity [19]. Based on these studies, we evaluated environments that conducive to possible interaction, such as social status, education, history of breastfeeding, and birth weight.…”

“…Results in a Mediterranean population suggest that education may modify the genetic susceptibility of FTO to obesity, with BMI being higher in non-university subjects compared to university subjects [18]. On the other hand, Pigeyre et al [19] report the influence of maternal education in the association of neuromedin B rs3809508 and the risk of obesity. Perinatal conditions, such as increased or decreased fetal growth, as measured by weight and height at birth, or low breastfeeding, may also influence the likelihood of obesity later on in life [20].…”