Universität zu Köln

Wipff, J., Dieude, P., Guedj, M., Ruiz, B., Riemekasten, G., Cracowski, J. L., Matucci-Cerinic, M., Melchers, I., Humbert, M., Hachulla, E., Airo, P., Diot, E., Hunzelmann, N., Caramaschi, P., Sibilia, J., Valentini, G., Tiev, K., Girerd, B., Mouthon, L., Riccieri, V., Carpentier, P. H., Distler, J., Amoura, Z., Tarner, I., Degano, B., Avouac, J., Meyer, O., Kahan, A., Boileau, C. and Allanore, Y. (2010). Association of a KCNA5 Gene Polymorphism With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension in the European Caucasian Population. Arthritis Rheum., 62 (10). S. 3093 - 3101. HOBOKEN: WILEY. ISSN 1529-0131

Full text not available from this repository.

Abstract

Objective. Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor beta receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. Methods. Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. Results. The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48-0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13-0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21-0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. Conclusion. Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wipff, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieude, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guedj, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruiz, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemekasten, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cracowski, J. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matucci-Cerinic, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Melchers, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humbert, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hachulla, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Airo, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diot, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunzelmann, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Caramaschi, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sibilia, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Valentini, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tiev, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Girerd, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mouthon, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riccieri, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Carpentier, P. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Distler, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Amoura, Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tarner, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Degano, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Avouac, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahan, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boileau, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Allanore, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494658
DOI:	10.1002/art.27607
Journal or Publication Title:	Arthritis Rheum.
Volume:	62
Number:	10
Page Range:	S. 3093 - 3101
Date:	2010
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1529-0131
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RISK-FACTOR; SUSCEPTIBILITY; SCLERODERMA; IRF5; PREDICTORS; MUTATIONS; CAPACITY; CHANNELS; OUTCOMES; SUBSETS Multiple languages Rheumatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49465