ERAP1 is associated with ankylosing spondylitis in Han Chinese.
ABSTRACT Genetic components play important roles in the incidence and development of ankylosing spondylitis (AS). Aminopeptidase regulator of tumor necrosis factor receptor shedding 1 (ERAP1) was recently found to be associated with AS in North American and British cohorts. We evaluated whether ERAP1 is associated with AS in a Chinese Han population.
A sample of 50 patients and 50 healthy controls was recruited for preliminary screening for informative single-nucleotide polymorphisms (SNP). Then 6 SNP of suggestive significance in the initial screening were followed up in a large sample of 471 patients with AS and 456 ethnically matched controls. Diagnosis of AS followed the 1984 modified New York criteria. Linkage disequilibrium coefficient (D' and r(2)) and haplotypes were estimated by Haploview. Result. Two SNP (rs27434, p = 0.00039, and rs27529, p = 0.0083) in ERAP1 other than that reported previously were found to be significantly associated with AS. Haplotype analysis using 5 SNP within 1 linkage disequilibrium block identified 2 risk haplotypes (GATGT and GACGT) and 1 protective haplotype (GGTGT) for AS.
Our study demonstrated that 2 novel SNP in ERAP1 were associated with AS in the Han Chinese population, suggesting that ERAP1 might confer genetic risk for AS in Han Chinese through the common mechanism shared by different populations, although the AS-associated SNP in ERAP1 might be population-specific.
Article: Spondyloarthritis in China.[show abstract] [hide abstract]
ABSTRACT: PURPOSE OF REVIEW: Although scientists in China have generated a considerable amount of new information about spondyloarthritis (SpA) in recent years, part of it was published in Chinese. The aim of this review is to summarize all SpA articles for the benefit of English readers. RECENT FINDINGS: In the field of epidemiology, prevalence of SpA in China has been updated, especially with regard to psoriatic arthritis (PsA). In the field of genetics, Chinese scientists have discovered new single-nucleotide polymorphism (SNP) sites association with ankylosing spondylitis (AS) in Han Chinese. In the field of treatment, tumour necrosis factor-alpha (TNF-α) antagonists are wildly used almost as a routine. The usefulness of certain Chinese traditional medicine is undergoing vigorous testing. In the field of diagnosis, ultrasound has been incorporated into the testing tools. In the field of monitoring of disease activity, Ankylosing Spondylitis Disease Activity Scores (ASDAS) has been validated in a cohort of Chinese SpA patients. SUMMARY: Chinese scientists are using cutting-edge technology in the fields of research, diagnosis and management in SpA. What is needed are new approaches that can accommodate the large variations in socioeconomic status of various localities in the vast Chinese continent.Current opinion in rheumatology 05/2013; · 4.60 Impact Factor
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ABSTRACT: Purpose. Ankylosing spondylitis (AS) is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population. Recent Findings. In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC), ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions. Summary. This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.Clinical and Developmental Immunology 01/2013; 2013:419357. · 3.06 Impact Factor
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ABSTRACT: We assessed the role played by the ERAP1 gene in Turkish patients with ankylosing spondylitis (AS) in terms of disease susceptibility, clinical manifestations, and disease severity. We included 150 consecutive AS patients who met the modified New York classification criteria and 150 healthy controls. We documented the presence of 10 ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 in these patients. ERAP1 SNPs were genotyped using competitive allele-specific polymerase chain reaction. Differences between genotype and allele frequencies were compared using the Pearson's Chi-square test. The associations between ERAP1 SNPs, on the one hand, and with disease severity and clinical findings, on the other, were determined. One SNP, rs26653, was significantly associated with AS susceptibility (OR 1.609, 95 % CI 1.163-2.226; p = 0.004). The population-attributable risk of possession of the rs26653 SNP allele was 23.4 %. No relationship was noted between HLA-B27 positivity and the distribution of rs26653 genotype frequency. No associations were seen between disease severity measures and clinical manifestations of AS. In summary, an ERAP1 polymorphism was associated with AS in a Turkish population. The contributions of HLA-B27 and the rs26653 SNP to AS pathogenesis appear to be independent.Rheumatology International 07/2013; · 2.21 Impact Factor