title: A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome in Swedes.
abstract: Metabolic syndrome (MetS) constitutes a worldwide epidemic burst accounting for billions of cardiovascular disease events and deaths. The genetic basis of MetS is largely unknown. The rs11646213 T → A polymorphism maps at 16q23.3 upstream of the CDH13 gene codifying for cadherin-13 (also known as T-cadherin or H-cadherin), which is considered a vascular adiponectin receptor. This and other single-nucleotide polymorphisms have been associated with hypertension and adiponectin level in separate studies. The aim of the present study was to evaluate the effect of the CDH13 rs11646213 T → A polymorphism on individual components of MetS and on MetS. The polymorphism was genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study (n = 4,942) and successively in the Malmö Preventive Project (n = 17,675) cohort at baseline and after an average of 23 years of follow-up (reinvestigation). Four different definitions of MetS were applied to these cohorts. In the cardiovascular arm, CDH13 rs11646213 AA homozygotic women showed a trend toward higher triglycerides and lower high-density lipoprotein cholesterol and presented a higher MetS score (composite sum of MetS phenotypes). MetS (Adult Treatment Panel III definition) was more prevalent in AA homozygotic women compared to T-carriers, a result confirmed in the Malmö Preventive Project cohort at baseline and at reinvestigation with an increased risk from 19% to 45% in AA homozygotic women. In conclusion, the CDH13 rs11646213 T > A polymorphism was consistently associated with MetS in Swedish women recruited in 2 large cohorts. In light of the role of cadherin-13 as a vascular receptor for adiponectin, our study supports the genetic basis for the role of adiponectin in MetS pathogenesis.
authors.affiliation: Department of Clinical Sciences, Lund University, University Hospital of Malmö, Malmö, Sweden. cristiano.fava@med.lu.se
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.forename: Elisa
authors.initials: E
authors.lastname: Danese
authors.forename: Martina
authors.initials: M
authors.lastname: Montagnana
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Guidi
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lechi
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000368:Aged; D015820:Cadherins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008593:Menopause; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D013548:Sweden / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
chemical_list: D015820:Cadherins; D008076:Cholesterol, HDL; C099972:H-cadherin; D014280:Triglycerides