Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

Danoy, P., Wei, M., Johanna, H., Jiang, L., He, D., Sun, L., Zeng, X., Visscher, P. M., Brown, Matthew A, & Xu, H. (2011) Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population. Annals of the Rheumatic Diseases, 70(10), pp. 1793-1797.

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The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations.


To investigate these associations in the Han Chinese population.


Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2 =0.8) across 19 distinct RA genomic regions. A two phase case-control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied.


Robust association was detected for MMEL1 and CTLA4 , and modest association was identified for another six loci: PADI4 , STAT4 , PRDM1 , CDK6 , TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10 -5unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4 , significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10-5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed.


This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

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ID Code: 87734
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: adult, article, CDK6 gene, Chinese, controlled study, CTLA4 gene, female, gene, gene locus, genetic association, genetic database, genotype, haplotype, human, KIF5A PIP4K2C gene, major clinical study, male, MMEL1 gene, PAD14 gene, population research, PRDM1 gene, priority journal, rheumatoid arthritis, single nucleotide polymorphism, STAT4 gene, TRAF1 C5 gene, Aged, Antigens, CD, Arthritis, Rheumatoid, Asian Continental Ancestry Group, Case-Control Studies, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Humans, Middle Aged, Neprilysin, Polymorphism, Single Nucleotide
DOI: 10.1136/ard.2010.144576
ISSN: 0003-4967
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 25 Sep 2015 00:05
Last Modified: 19 Aug 2016 04:28

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