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J Rheumatol. 2014 Feb;41(2):318-24. doi: 10.3899/jrheum.130519. Epub 2013 Dec 15.

Evidence for genetic association of CARD9 and SNAPC4 with ankylosing spondylitis in a Chinese Han population.

Author information

1
From the Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine; Institute of Basic Medicine, Shandong Academy of Medical Science, Jinan, Shandong; Institute of Geriatrics, Beijing Hospital, Ministry of Health of People's Republic of China (PRC), Beijing, China.

Abstract

OBJECTIVE:

A genome-wide association study and 2 replication studies identified 2 single-nucleotide polymorphisms (SNP) of caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) at Chr 9q34.3 associated with ankylosing spondylitis (AS) in whites. We explored a possible association of SNP in CARD9 and SNAPC4 and AS in a Chinese Han population from Shandong.

METHODS:

The study included 1150 patients with AS and 1120 healthy controls who underwent genotyping for 4 SNP of CARD9 and 2 of SNAPC4; we replicated the results in another 490 patients and 380 healthy controls of Ningxia Han Chinese during the same time. We used quantitative real-time PCR (qRT-PCR) to measure CARD9 and SNAPC4 mRNA expression in peripheral leukocytes from 44 patients and 36 controls and allele-specific mRNA expression of CARD9 and SNAPC4 in leukocytes from 130 controls.

RESULTS:

We validated that an SNP in SNAPC4, rs11145835, was significantly associated with AS in our Chinese Han population (p = 0.001) and replicated the association in samples from the Chinese Ningxia Han population (p = 0.002). Carrying the G allele of rs11145835 was associated with increased risk of AS (OR 1.34, 95% CI 1.12-1.59) and with decreased expression of CARD9 (p = 0.001) and SNAPC4 (p = 0.02) in leukocytes. SNAPC4 mRNA expression was lower in leukocytes from patients than from controls (p = 0.0002).

CONCLUSION:

Our study confirmed that an SNP rs11145835 in 9q34.3 that harbors CARD9 and SNAPC4 is associated with AS in a Chinese Han population, and rs11145835 in SNAPC4 is a potential causal variant.

KEYWORDS:

ANKYLOSING SPONDYLITIS; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 9; SINGLE NUCLEOTIDE POLYMORPHISMS; SMALL NUCLEAR RNA-ACTIVATING COMPLEX POLYPEPTIDE 4

PMID:
24334645
DOI:
10.3899/jrheum.130519
[Indexed for MEDLINE]

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