BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inborn disorder of the connective tissue with specific skin, ocular, and cardiovascular disease (CVD) manifestations. Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement. In the Netherlands, as in the rest of Europe, a particular premature truncation variant ABCC6 (R1141X) was found in a large cohort of PXE patients. Given the association between CVD and PXE, we hypothesized that heterozygosity of this ABCC6 mutation could also confer an increased risk for CVD. METHODS AND RESULTS: To assess the relationship between the frequent R1141X mutation in the ABCC6 gene and the prevalence of premature coronary artery disease (CAD), we conducted a case-control study of 441 patients under the age of 50 years who had definite CAD and 1057 age- and sex-matched population-based controls who were free of coronary disease. Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls (3.2% versus 0.8%; P<0.001). Consequently, among subjects with the R1141X mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to 10.20, P= 0.001). CONCLUSION: The presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature CAD.
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inborn disorder of the connective tissue with specific skin, ocular, and cardiovascular disease (CVD) manifestations. Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement. In the Netherlands, as in the rest of Europe, a particular premature truncation variant ABCC6 (R1141X) was found in a large cohort of PXE patients. Given the association between CVD and PXE, we hypothesized that heterozygosity of this ABCC6 mutation could also confer an increased risk for CVD. METHODS AND RESULTS: To assess the relationship between the frequent R1141X mutation in the ABCC6 gene and the prevalence of premature coronary artery disease (CAD), we conducted a case-control study of 441 patients under the age of 50 years who had definite CAD and 1057 age- and sex-matched population-based controls who were free of coronary disease. Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls (3.2% versus 0.8%; P<0.001). Consequently, among subjects with the R1141X mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to 10.20, P= 0.001). CONCLUSION: The presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature CAD.
Authors: Paolo Cerrato; M Giraudo; C Baima; M Grasso; C Azzaro; A Lentini; P Perozzo; G Doveil; B Bergamasco Journal: J Neurol Date: 2005-03-17 Impact factor: 4.849
Authors: Arthur A B Bergen; Astrid S Plomp; Xiaofeng Hu; Paulus T V M de Jong; Theo G M F Gorgels Journal: Pflugers Arch Date: 2006-04-08 Impact factor: 3.657
Authors: Shiping Liu; Eline D Lorenzen; Matteo Fumagalli; Bo Li; Kelley Harris; Zijun Xiong; Long Zhou; Thorfinn Sand Korneliussen; Mehmet Somel; Courtney Babbitt; Greg Wray; Jianwen Li; Weiming He; Zhuo Wang; Wenjing Fu; Xueyan Xiang; Claire C Morgan; Aoife Doherty; Mary J O'Connell; James O McInerney; Erik W Born; Love Dalén; Rune Dietz; Ludovic Orlando; Christian Sonne; Guojie Zhang; Rasmus Nielsen; Eske Willerslev; Jun Wang Journal: Cell Date: 2014-05-08 Impact factor: 41.582