Functional glucokinase regulator gene variants have inverse effects on triglyceride and glucose levels, and decrease the risk of obesity in children.

OBJECTIVE: Recently, the association of the natural variants rs1260326 and rs780094 of the glucokinase regulatory protein (GCKR) gene with increased fasting triglycerides and decreased fasting plasma glucose in diabetic adults was reported; the minor alleles were also found to reduce the risk of type 2 diabetes. The present study examined the possible associations of these variants with triglycerides and glucose levels, their allele distribution and their possible effects on childhood obesity. METHODS AND RESULTS: A total of 221 obese children and 115 healthy normal-weight children as controls were genotyped using PCR-RFLP methods. Both functional GCKR variants were found in association with elevated serum triglycerides and lower fasting plasma glucose levels. Results of logistic regression revealed that, despite higher triglyceride levels, the carriers of the GCKR variants were more protected against the development of obesity; the adjusted models confirmed the lower risk of obesity for both variants (rs1260326: OR, 0.46; 95% CI, 0.25-0.83; rs780094: OR, 0.41; 95% CI, 0.23-0.74). CONCLUSION: Our findings confirm the inverse modulating effect of functional GCKR variants on triglycerides and glucose levels in obese paediatric patients and healthy normal-weight controls. The results of our study strongly suggest that the minor alleles confer protection against the development of obesity in children. The findings also suggest that the minor alleles of functional GCKR may protect against diabetes and the metabolic syndrome in adults.

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

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=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=0.05; adjusted odds ratio for obesity (95% confidence interval): 2.85 (1.11-7.31), P=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=0.02), waist circumference (75.8+/-9.7 cm vs 72.2+/-9.3 cm, P=0.006), waist-to-hip ratio (0.84+/-0.14 vs 0.79+/-0.07, P<0.0001) and waist-to-height ratio (0.47+/-0.06 vs 0.44+/-0.55, P=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: P<0.02). 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=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.