TY - JOUR
T1 - No evidence for an involvement of variants in the cannabinoid receptor gene (CNR1) in obesity in German children and adolescents
AU - Müller, Timo Dirk
AU - Reichwald, Kathrin
AU - Wermter, Anne Kathrin
AU - Brönner, Günter
AU - Nguyen, Thuy Trang
AU - Friedel, Susann
AU - Koberwitz, Kerstin
AU - Engeli, Stefan
AU - Lichtner, Peter
AU - Meitinger, Thomas
AU - Schäfer, Helmut
AU - Hebebrand, Johannes
AU - Hinney, Anke
N1 - Funding Information:
This work was supported by grants from the Federal Ministry of Education and Research (NGFN2; 01GS0482, 01GS0483), the European Union (FP6 LSHMCT-2003-503041) and by the Deutsche Forschungsgesellschaft (DFG; HE 1446/4-1).
Funding Information:
The skilful and diligent technical assistance of Jitka Andrä and Gerti Gerber is gratefully acknowledged. Patient assessment was financed by the German Research Foundation. This work was supported by grants from the Federal Ministry of Education and Research (NGFN2; 01GS0482, 01GS0483), the European Union (FP6 LSHMCT-2003-503041) and by the Deutsche Forschungsgesellschaft (DFG; HE 1446/4-1).
PY - 2007/4
Y1 - 2007/4
N2 - Studies in rodent models demonstrated that the central cannabinoid receptor (Cnr1) mediates the orexigenic effects of cannabinoids. To analyze whether genetic variation in the cannabinoid receptor gene (CNR1) is implicated in human obesity, we initially genotyped 8 single nucleotide polymorphisms (SNPs) located in the 5′ region (rs9353527, rs754387, rs6454676), intron 2 (rs806379, rs1535255), exon 3 (rs2023239), intron 3 (rs806370) and the coding region (rs1049353) in up to 364 German obesity trios (extremely obese child or adolescent and both parents). The transmission disequilibrium test (TDT) was negative for these SNPs (p > 0.05). However, there was a slight trend towards preferential transmission of the A-allele of rs1049353 (p = 0.12). We therefore genotyped this SNP in 235 independent German obesity families (at least two obese sibs and both parents) and in parallel screened the CNR1 coding region for sequence variations in 120 German extremely obese children and adolescents who mainly contributed to the initial trend observed for rs1049353. The trend for preferential transmission of the A-allele could not be substantiated (pedigree disequilibrium test, PDT p = 0.15; A-allele less frequently transmitted). In the mutation screen we detected two rare variations, one novel non-conservative mutation (c.1256C>A; A419E) and the known variant 1419+1G>C. In addition, we confirmed the presence of rs1049353. As these variants could not explain the initial TDT, we conclude that there is no evidence for an association of CNR1 alleles with obesity in our study groups.
AB - Studies in rodent models demonstrated that the central cannabinoid receptor (Cnr1) mediates the orexigenic effects of cannabinoids. To analyze whether genetic variation in the cannabinoid receptor gene (CNR1) is implicated in human obesity, we initially genotyped 8 single nucleotide polymorphisms (SNPs) located in the 5′ region (rs9353527, rs754387, rs6454676), intron 2 (rs806379, rs1535255), exon 3 (rs2023239), intron 3 (rs806370) and the coding region (rs1049353) in up to 364 German obesity trios (extremely obese child or adolescent and both parents). The transmission disequilibrium test (TDT) was negative for these SNPs (p > 0.05). However, there was a slight trend towards preferential transmission of the A-allele of rs1049353 (p = 0.12). We therefore genotyped this SNP in 235 independent German obesity families (at least two obese sibs and both parents) and in parallel screened the CNR1 coding region for sequence variations in 120 German extremely obese children and adolescents who mainly contributed to the initial trend observed for rs1049353. The trend for preferential transmission of the A-allele could not be substantiated (pedigree disequilibrium test, PDT p = 0.15; A-allele less frequently transmitted). In the mutation screen we detected two rare variations, one novel non-conservative mutation (c.1256C>A; A419E) and the known variant 1419+1G>C. In addition, we confirmed the presence of rs1049353. As these variants could not explain the initial TDT, we conclude that there is no evidence for an association of CNR1 alleles with obesity in our study groups.
KW - Association study
KW - Cannabinoid-receptor 1
KW - Early onset obesity
UR - http://www.scopus.com/inward/record.url?scp=33947586983&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2007.01.002
DO - 10.1016/j.ymgme.2007.01.002
M3 - Article
C2 - 17292652
AN - SCOPUS:33947586983
SN - 1096-7192
VL - 90
SP - 429
EP - 434
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 4
ER -
