A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome in Swedes.

Metabolic syndrome (MetS) constitutes a worldwide epidemic burst accounting for billions of cardiovascular disease events and deaths. Genetic basis of MetS is largely unknown. The rs11646213 T>A polymorphism maps at 16q23.3 upstream of the CDH13 gene codifying for the cadherin 13 (also known as T-cadherin or H-cadherin), which is considered a vascular adiponectin receptor. This and other SNPs have been associated with both hypertension and adiponectin level in separate studies. The aim of the present study was to evaluate the effect of the CDH13 rs11646213 T>A, on the individual components of MetS and MetS itself. The polymorphism was genotyped in the cardiovascular cohort of the Malmö Diet and Cancer (MDC-CVA; n=4,942) study and successively in the Malmö Preventive Project (MPP; n=17,675) cohort both at baseline and after an average of 23 years of follow-up (reinvestigation). Four different definitions of the MetS were applied on all these cohorts. In the MDC-CVA, female CDH13 rs11646213 AA-homozygotes showed a trend toward higher triglycerides and lower HDL-cholesterol and presented a higher MetS score (a composite sum of MetS phenotypes). MetS (ATPIII definition) was more prevalent in female AA-homozygotes with respect to T-carriers, a result confirmed in the MPP cohort both at baseline and at reinvestigation with an increased risk ranging from 19 to 45% in female AA-homozygotes. In conclusion the CDH13 rs11646213 T>A polymorphism is consistently associated with MetS in Swedish women recruited in 2 large cohorts. On the 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.