Association Study On Killer Cell Immunoglobulin-like Receptor (KIR) Genes Polymorphisms And Gene-environment Interaction In Ankylosing Spondylitis

Objective Being a rheumatic arthritis, ankylosing spondylitis is one of the most common autoimmune diseases, which causes axial inflammation and affects extra-articular sites, with an estimated prevalence of 0.1%-0.9%. Substantial evidence revealed that the pathogenesis of AS is associated with the interaction of complex genetic factors, environmental factors and autoimmune disorders. Recent studies explored the role of Killer cell Immunoglobulin-like Receptor(KIR) playing in chronic autoimmune diseases. This study will investigate the possible association between KIR genes polymorphisms and ankylosing spondylitis, and the interaction of gene and environment in AS.Methods A total for 16 KIR genes was genotyped from 120 unrelated samples. The study samples consisted of 60 B27-positive Chinese patients with AS who were selected from Department of Rheumatology, First Affiliated Hospital of Anhui Medical University and 60 B27-positive healthy control subjects. We also study the HLA-B27 subtypes of the 60 AS cases. Clinical diagnosis of AS was carried out strictly according to the modified New York criteria. DNA was prepared from peripheral blood leucocytes by standard methods. Polymerase chain reaction-sequence specific primer ( PCR-SSP) methods were used in KIR genotyping and HLA-B27 subtyping. All the samples need All the samples in our study answered the questionnaire, which including individual essential information, habits and customs, Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Disease Activity Index(BASDAI). Different frequencies of KIR genotypes between AS and controls were assessed by usingχ~2 test, and a case-only study was used for analyzing interactions between KIR and environment.Results The 60 B27-positive AS patients consisted of 46 males and 14 females, and the average age is 31.00±8.38. The 60 B27-positive healthy control subjects consisted of 44 males and 16 females,and the average age is 29.31±7.42. We found that sexual differences were associated with BASFI and BASDAI(all P<0.05). All the 16 KIR genes were detected in the 120 samples, including 2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, pseudogene 2DP1 and 3DP1. Five B27 subtypes had been found in 60 AS cases, including B*2704(33, 55%), B*2705(24, 40%), B*2702(1, 1.67%), B*2710(1, 1.67%) and B*2715(1, 1.67%). The KIR3DS1 frequency had showed a significant difference (χ~2 =5.263, P=0.006, OR=3.059, 95%CI=1.357~6.896) between AS cases and healthy controls. There is an interaction between KIR3DS1 and living in noisy environment (P=0.017, OR=4.709, 95%CI=1.245~17.813) and there isn't any interaction between KIR3DS1 and B27 subtypes.Conclusions All the 16 KIR genes were found in the 120 samples, and five HLA-B27 subtypes were also found in patients with AS. KIR3DS1 may play an important role in pathogenesis of AS, and it do not associate with HLA-B27 subtypes. Sexual differences may affect the scores of BASFI and BASDAI. Living in noisy environment may take an interaction with activating KIR3DS1 to enhance the susceptibility to AS. The health education of ankylosing spondylitis in a crowd of young peoples who had a manual work shows a great significance to AS for prevention and control.