Association of Cullin1 haplotype variants with rheumatoid arthritis and response to methotrexate.

Abstract:

:Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has been associated with RA etiology and drug response, respectively. We carried out a replication study of association of CUL1 polymorphisms with RA in a north Indian population. Allelic, genotypic, and haplotypic associations of a promoter and two intronic polymorphisms of CUL1 with RA and with methotrexate response in patients with RA, were tested. A significant association (P=0.00056, adjusted) of a haplotype A-T-T with RA (odds ratio=3.68; 95% confidence interval=1.86-7.27) and in patients with RA poorly responding to methotrexate treatment (P=0.04, adjusted) was observed. Association with CUL1 haplotype indicates a possible role of CUL1 variation(s) in RA and its response to methotrexate.

journal_name

Pharmacogenet Genomics

authors

Negi S,Kumar A,Thelma BK,Juyal RC

doi

10.1097/FPC.0b013e3283492af7

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

590-3

issue

9

eissn

1744-6872

issn

1744-6880

journal_volume

21

pub_type

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