ABCMdb

PMID: 12176944

Trip MD, Smulders YM, Wegman JJ, Hu X, Boer JM, ten Brink JB, Zwinderman AH, Kastelein JJ, Feskens EJ, Bergen AA
Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease.
Circulation. 2002 Aug 13;106(7):773-5., 2002-08-13 [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC6 p.Arg1141* Feskens and Arthur A.B. Bergen Boer, Jacoline B. ten Brink, Aeilko H. Zwinderman, John J.P. Kastelein, Edith J.M. Mieke D. Trip, Yvo M. Smulders, Jurgen J. Wegman, Xiaofeng Hu, Jolanda M.A. Increase in the Prevalence of Coronary Artery Disease Frequent Mutation in the ABCC6 Gene (R1141X) Is Associated With a Strong ISSN: 1524-4539 Copyright (c) 2002 American Heart Association. Login to comment 7 ABCC6 p.Arg1141* Fax: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters http://circ.ahajournals.org//subscriptions/ Subscriptions: Information about subscribing to Circulation is online at at UNIV OF N CAROLINA CHAPEL HILL on August 8, 2011http://circ.ahajournals.org/Downloaded from Frequent Mutation in the ABCC6 Gene (R1141X) Is Associated With a Strong Increase in the Prevalence of Coronary Artery Disease Mieke D. Trip, MD; Yvo M. Smulders, MD, PhD; Jurgen J. Wegman, MD; Xiaofeng Hu, MD; Jolanda M.A. Boer, PhD; Jacoline B. ten Brink, Ing; Aeilko H. Zwinderman, PhD; John J.P. Kastelein, MD, PhD; Edith J.M. Feskens, PhD; Arthur A.B. Bergen, PhD Background-Pseudoxanthoma elasticum (PXE) is an inborn disorder of the connective tissue with specific skin, ocular, and cardiovascular disease (CVD) manifestations. Login to comment 9 ABCC6 p.Arg1141* 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. Login to comment 11 ABCC6 p.Arg1141* 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. Login to comment 12 ABCC6 p.Arg1141* Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls (3.2% versus 0.8%; PϽ0.001). Login to comment 13 ABCC6 p.Arg1141* Consequently, among subjects with the R1141X mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to 10.20, Pϭ0.001). Login to comment 14 ABCC6 p.Arg1141* Conclusion-The presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature CAD. Login to comment 22 ABCC6 p.Arg1141* In parallel studies (Xiaofeng Hu, unpublished data), we found that the R1141X mutation is the most common mutation in Dutch PXE patients and families, and it seems as though this is the case for the rest of Europe as well. Login to comment 23 ABCC6 p.Arg1141* We therefore studied the prevalence of the R1141X mutation in the ABCC6 gene in patients with premature CAD and in a large population-based group of healthy controls to further delineate the role of this genetic variation as a risk factor for CAD. Login to comment 51 ABCC6 p.Arg1141* In cases, 14 of 441 (3.2%, 95% CI: 1.9 to 5.6) were carriers of the R1141X truncation variant, whereas 8 of 1057 controls (0.8%, 95% CI: 0.3 to 1.5) carried this ABCC6 mutation, yielding a statistically significant difference at a probability value Ͻ0.001 with an odds ratio corrected for age and sex of 4.23 (95% CI: 1.76 to 10.20). Login to comment 52 ABCC6 p.Arg1141* We subsequently categorized the premature CAD patients in carriers (nϭ14) and noncarriers (nϭ427) of the R1141X variant of the ABCC6 gene (Table 2). Login to comment 54 ABCC6 p.Arg1141* Discussion We demonstrate in a large case-control study that a strong association exists between a frequent mutation in the ABCC6 gene (R1141X) and the presence of premature CAD. Login to comment 64 ABCC6 p.Arg1141* Baseline Characteristics of Patients According to R1141X Genotype Variable Heterozygous nϭ14 Wild Type nϭ427 P Age, y 48.1Ϯ6.0 47.3Ϯ6.0 0.64 Male sex 10 (71) 322 (80) 0.43 Age at diagnosis 39.6Ϯ6.9 40.6Ϯ6.1 0.56 History of MI 11 (79) 312 (78) 0.93 Smoking 4 (29) 113 (28) 0.84 BMI, kg/m2 26.4Ϯ3.6 26.8Ϯ4.0 0.71 Hypertension 8 (57) 145 (36) 0.13 DM II 6 (43) 111 (27) 0.13 Family history CAD 9 (64) 229 (57) 0.33 Total cholesterol, mmol/L 5.96Ϯ1.36 5.81Ϯ1.60 0.73 HDL cholesterol, mmol/L 1.01Ϯ0.17 1.10Ϯ0.31 0.29 LDL cholesterol, mmol/L 3.96Ϯ1.27 3.82Ϯ1.53 0.74 Triglycerides, mmol/L 2.19Ϯ1.43 2.09Ϯ2.12 0.43 Values are meanϮSD or n (%). Login to comment