RGD Reference Report - Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population. - Rat Genome Database

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

Authors: Danoy, Patrick  Wei, Meng  Johanna, Hadler  Jiang, Lei  He, Dongyi  Sun, Linyun  Zeng, Xiaofeng  Visscher, Peter M  Brown, Matthew A  Xu, Huji 
Citation: Danoy P, etal., Ann Rheum Dis. 2011 Oct;70(10):1793-7. doi: 10.1136/ard.2010.144576. Epub 2011 Jul 21.
RGD ID: 12793073
Pubmed: PMID:21784728   (View Abstract at PubMed)
DOI: DOI:10.1136/ard.2010.144576   (Journal Full-text)


BACKGROUND: 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.
OBJECTIVE: To investigate these associations in the Han Chinese population.
METHODS: Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r(2)=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.
RESULTS: 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(-5) unadjusted, 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.
CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
rheumatoid arthritis  IAGP 12793073DNA:snps:intron more ...RGD 
rheumatoid arthritis  ISOKIF5A (Homo sapiens)12793073; 12793073DNA:snps:intron more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Joint stiffness  IAGP 12793073DNA:snps:intron more ...RGD 
Soft tissue swelling of interphalangeal joints  IAGP 12793073DNA:snps:intron more ...RGD 
Swelling of proximal interphalangeal joints  IAGP 12793073DNA:snps:intron more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Kif5a  (kinesin family member 5A)

Genes (Mus musculus)
Kif5a  (kinesin family member 5A)

Genes (Homo sapiens)
KIF5A  (kinesin family member 5A)


Additional Information