A Variant Upstream of the CDH13 Adiponectin Receptor Gene and Metabolic Syndrome in Swedes

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• 作者：Cristiano  ; Fava MD ; PhD^a ;   ; ^c ;   ; ^{cristiano.fava@med.lu.se} ; Elisa  ; Danese PharmD^a ;   ; ^d ;   ; ^&dagger ; ; Martina  ; Montagnana MD^a ;   ; ^d ;   ; ^&dagger ; ; Marketa  ; Sjö ; gren PhD^a ; Peter  ; Almgren MSc^a ; Gian Cesare  ; Guidi MD^d ; Bo  ; Hedblad MD ; PhD^a ;   ; ^b ; Gunnar  ; Engströ ; m MD ; PhD^a ; Alessandro  ; Lechi MD^c ; Pietro  ; Minuz MD^c ; Olle  ; Melander MD ; PhD^a
• 刊名：The American Journal of Cardiology
• 出版年：2011
• 出版时间：15 November 2011
• 年：2011
• 卷：108
• 期：10
• 页码：1432-1437
• 全文大小：184 K

文摘

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 Malm? Diet and Cancer Study (n = 4,942) and successively in the Malm? 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 Malm? 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.