title: CDH13 gene coding T-cadherin influences variations in plasma adiponectin levels in the Japanese population.
abstract: Adiponectin is most abundantly expressed in adipose tissue and well known to play an important role in metabolic regulation. Several studies have attempted to identify the genetic determinants of metabolic syndrome (MetS), though no study has revealed a cis- or trans-single nucleotide polymorphism (SNP) that affects plasma adiponectin levels, except the adiponectin structure gene and genes encoding adiponectin-regulatory proteins. We performed a genome-wide association study in regards to plasma adiponectin concentrations in 3,310 Japanese subjects. We identified the strongest statistically associated SNP (rs4783244) with adiponectin levels (P = 3.8 × 10(-19)) in the first intron of CDH13 (T-cadherin) gene in a 30-kb haplotype block covering the promoter region to first intron. In addition, rs12051272 SNP genotypes in linkage disequilibrium with rs4783244 were found to be more significantly associated with adiponectin levels (P = 9.5×10(-20)) and specifically with the levels of high-molecular weight (HMW) adiponectin, a subtype form associated with parameters related to glucose metabolism. Our results did show more significant association with adiponectin levels than rs12444338 (in CDH13) SNP genotypes reported recently. We suggest that the phenotype-affecting haplotype tagged by rs12051272 SNP would affect the plasma adiponectin levels and that we have to take the CDH13 genotype into account before considering the functional relevance of the adiponectin level.
authors: Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors: Hiroko
authors: H
authors: Morisaki
authors: Itaru
authors: I
authors: Yamanaka
authors: Naoharu
authors: N
authors: Iwai
authors: Yoshihiro
authors: Y
authors: Miyamoto
authors: Yoshihiro
authors: Y
authors: Kokubo
authors: Tomonori
authors: T
authors: Okamura
authors: Akira
authors: A
authors: Okayama
authors: Takayuki
authors: T
authors: Morisaki
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin