ABSTRACT
The neuropeptide galanin (GAL) is involved in food intake and in fat ingestion. Presumably, these effects are conveyed via the galanin 1 receptor (GALR1). We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students). In GAL, we identified 3 novel single nucleotide polymorphisms (SNPs; silent: g.-419T-->C, g.-244G-->A; missense: g.47C-->T: Ala16Val) and one infrequent missense variation (c.253A-->G: Asn85Asp), and in GALR1 2 novel SNPs (silent: c.150C-->T, missense: c.793A-->T: Ile265Phe). To test for an association with obesity, we genotyped 7 SNPs (GAL: g.-244G-->A, g.47C-->T, rs7101947, rs1042577, rs3136540; GALR1: c.150C-->T, c.793A-->T) in up to 322 obese children and adolescents compared with up to 277 healthy underweight and normal weight young adults. Furthermore, we analyzed these SNPs with respect to potential effects on the percentage of energy consumed as fat in obese children and adolescents. Allele and genotype frequencies did not differ among the groups tested. In addition, we performed a pedigree transmission disequilibrium test (PDT) for one SNP (GAL: g.-244G-->A) in 610 (518 independent) obesity-trios (obese child or adolescent and both of its parents). However, the PDT for SNP GAL g.-244G-->A revealed no transmission disequilibrium. We conclude that the analyzed SNPs in GAL and GALR1 do not play a major role in early onset obesity or dietary fat intake in the obese children and adolescents of our study groups.
Subject(s)
Dietary Fats/administration & dosage , Eating/physiology , Galanin/physiology , Genetic Variation , Obesity/etiology , Receptor, Galanin, Type 1/physiology , Adolescent , Adult , Case-Control Studies , Child , Eating/genetics , Female , Galanin/genetics , Humans , Male , Polymorphism, Single Nucleotide , Receptor, Galanin, Type 1/geneticsABSTRACT
GH secretagogue receptor (GHSR, ghrelin receptor) is involved in regulation of body weight and GH secretion. We initially analyzed two single-nucleotide polymorphisms of the GHSR in up to 184 extremely obese children and adolescents and up to 184 healthy underweight students. The frequency of the 171T allele of rs495225 was higher in our obese samples (75.0%) than in the underweight individuals (70.2%; nominal P = 0.14). This trend could not be substantiated in an additional association study in 270 obese and 145 underweight and normal weight individuals and in a transmission disequilibrium test based on 387 obesity trios (transmission rate of 171T, 51.8%; nominal P = 0.53). Additionally, the coding region of GHSR was systematically screened, and seven sequence variants were identified in 93 obese, 96 normal weight, and 94 underweight individuals and 43 children with short normal stature (SNS). Five silent single-nucleotide polymorphisms showed similar genotype frequencies in the different weight groups and SNS children (all nominal P > 0.3). Two novel missense variants were detected only in one obese carrier and one SNS child, respectively. In conclusion, we did not obtain conclusive evidence for an involvement of the ghrelin receptor gene in body weight regulation or SNS in our study groups.
Subject(s)
Body Height , Body Weight , Obesity/genetics , Polymorphism, Single Nucleotide , Receptors, G-Protein-Coupled/genetics , Adolescent , Adult , Alleles , Child , Female , Gene Frequency , Genotype , Humans , Male , Mutation, Missense , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded Conformational , Receptors, Ghrelin , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , StudentsABSTRACT
OBJECTIVE: Several genome scans have been performed for adult obesity. Because single formal genetic studies suggest a higher heritability of body weight in adolescence and because genes that influence body weight in adulthood might not be the same as those that are relevant in childhood and adolescence, we performed a whole genome scan. METHODS: The genome scan was based on 89 families with 2 or more obese children (sample 1). The mean age of the index patients was 13.63 +/- 2.75 years. A total of 369 individuals were initially genotyped for 437 microsatellite markers. A second sample of 76 families was genotyped using microsatellite markers that localize to regions for which maximum likelihood binomial logarithm of the odd (MLB LOD) scores on use of the concordant sibling pair approach exceeded 0.7 in sample 1. RESULTS: The regions with MLB LOD scores >0.7 were on chromosomes 1p32.3-p33, 2q37.1-q37.3, 4q21, 8p22, 9p21.3, 10p11.23, 11q11-q13.1, 14q24-ter, and 19p13-q12 in sample 1; MLB LOD scores on chromosomes 8p and 19q exceeded 1.5. In sample 2, MLB LOD scores of 0.68 and 0.71 were observed for chromosomes 10p11.23 and 11q13, respectively. CONCLUSION: We consider that several of the peaks identified in other scans also gave a signal in this scan as promising for ongoing pursuits to identify relevant genes. The genetic basis of childhood and adolescent obesity might not differ that much from adult obesity.
