Evidence for genetic association of CARD9 and SNAPC4 with ankylosing spondylitis in a Chinese Han population.
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.
['Ma|Xiaochun|X|', 'Liu|Yongchao|Y|', 'Zhang|Hua|H|', 'Qiu|Rongfang|R|', 'Zhao|Hailing|H|', 'Xin|Qian|Q|', 'Shan|Shan|S|', 'Dang|Jie|J|', 'Li|Jiangxia|J|', 'Yang|Ze|Z|', 'Gong|Yaoqin|Y|', 'Liu|Qiji|Q|']
D000328:Adult D000483:Alleles D044466:Asians D053468:CARD Signaling Adaptor Proteins D016022:Case-Control Studies D004268:DNA-Binding Proteins D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D005838:Genotype D006239:Haplotypes D006801:Humans D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D013167:Spondylitis, Ankylosing D014157:Transcription Factors D055815:Young Adult
ANKYLOSING SPONDYLITIS CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 9 SMALL NUCLEAR RNA-ACTIVATING COMPLEX POLYPEPTIDE 4 SINGLE NUCLEOTIDE POLYMORPHISMS