title: Evidence for genetic association of CARD9 and SNAPC4 with ankylosing spondylitis in a Chinese Han population.
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).
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Xiaochun
authors: X
authors: Ma
authors: Yongchao
authors: Y
authors: Liu
authors: Hua
authors: H
authors: Zhang
authors: Rongfang
authors: R
authors: Qiu
authors: Hailing
authors: H
authors: Zhao
authors: Qian
authors: Q
authors: Xin
authors: Shan
authors: S
authors: Shan
authors: Jie
authors: J
authors: Dang
authors: Jiangxia
authors: J
authors: Li
authors: Ze
authors: Z
authors: Yang
authors: Yaoqin
authors: Y
authors: Gong
authors: Qiji
authors: Q
authors: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; 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 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D004268:DNA-Binding Proteins; C116351:SNAPC4 protein, human; D014157:Transcription Factors
keywords: ANKYLOSING SPONDYLITIS; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 9; SINGLE NUCLEOTIDE POLYMORPHISMS; SMALL NUCLEAR RNA-ACTIVATING COMPLEX POLYPEPTIDE 4