| Ankylosing spondylitis (AS) is a debilitating chronic inflammatory condition with a high degree of familiality and heritability that primarily affects spinal and sacroiliac joints. The elucidation of the genetic determinants will lead to a better understanding of disease pathogenesis, and enhanced prediction of disease risk, diagnosis, prognosis, and therapy. The cause of ankylosing spondylitis (AS) still remains unelucidated. Both genetic and environmental factors are suspected playing an important role in AS development. Peptidyl arginine deiminase, type IV (PADI4) is a member of a gene family which encodes enzymes responsible for the conversion of arginine to citrulline residues playing a pivotal role in bone mass and metabolism. Previously a strong linkage between PADI4 polymorphism and rheumatoid arthritis (RA) has been found in Japanese patients but there were very rare association study between PADI4 and AS.In this study a total of 316 Chinese AS patients of Han nationality and 439 healthy controls were recruited. Five single-nucleotide polymorphisms (SNPs), PADI4-89 A/G (rs11203366), PADI4-90 (rs11203367) C/T, PADI4-92 (rs874881) C/G, PADI4-94 C/T (rs2240340) and PADI4-104 C/T (rs1748033), in the PADI4 gene were selected and the allele frequencies between cases and controls were assessed. The major allele frequency of the five SNPs in case-control is 0.57 vs 0.60,0.57 vs 0.59,0.57 vs 0.57,0.45 vs 0.42,0.61 vs 0.62, respectively. The frequency sum of the two major haplotype (ACCGC, GTGAT) was accounded 85.7% in cases and 83.7% in controls. No significant differences in the frequency of PADI4 alleles, genotypes and haplotypes were observed between the cases and controls. PADI4 gene polymorphism is not associated with ankylosing spondylitis in Chinese Han population.Rheumatoid arthritis (RA) is a complex disease which arises from interplay between genetic and environmental factors. Despite lots of advances in the treatment was achieved recently, the etiology of RA still remains elusive. Non-major histocompatibility complex genes have been identified and novel technologies promise that a more thorough examination of the rest of the genome will soon elucidate the genetic basis of this disease. This PADI4 gene is commonly expressed in RA synovial tissues reported by some studies. In this study we also investigate the five SNPs as PADI4 as PADI4-89 (rsl 1203366), PADI4-90 (rs11203367), PADI4-92 (rs874881), PADI4-94 (rs2240340) and PADI4-104 (rs1748033) in 378 unrelated patients with RA (cases) and 204 healthy individuals (controls) of Chinese Han population. The major allele frequency of the five SNPs in case-control is 0.55 vs 0.56,0.55 vs 0.57,0.57 vs 0.62,0.54 vs 0.55,0.60 vs 0.60, respectively. The frequency sum of the two major haplotype (ACCCC, GTGTT) was accounded 76.8% in case and 81.5% in controls. There were no significant differences in the frequency of PADI4 alleles, genotypes and haplotypes between RA cases and controls. The results indicate that PADI4 polymorphisms do not play an important role in the development of AS in Chinese Han population.The polymorphism of PADI4 gene might differ in different populations. To a homogeneous multigene disorders like AS and RA, PADI4 only plays a little part in the course of disease and the polymorphism of PADI4 gene differ in different populations. At the same time, many genetic and environmental factors involved in AS or RA onset and development. In an attempt to elucidate the etiology of AS or RA, the further association studies involving more cases and different ethnic groups will be required. In the post-genome era, the Genome-wide association study (GWAS) is a powerful tool in discovering clues to AS and RA, and indicate some directions for association study. Our research results suggested that the PADI4 gene is not associzted with AS and RA in Chinese Han population. Its association to other autoimmunological diseases needs further investigation. |
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