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

作者：Negi Sapna; Kumar Ashok; Thelma B K; Juyal Ramesh C^*

来源：Pharmacogenetics and Genomics, 2011, 21(9): 590-593.

DOI：10.1097/FPC.0b013e3283492af7

• association study
• Cullin1
• methotrexate
• rheumatoid arthritis
• ubiquitination

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 I kappa B alpha 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.

• 出版日期2011-9