Association Between HRH4 Polymorphisms And Ankylosing Spondylitis Susceptibility

Background:Ankylosing Spondylitis(AS) is chronic inflammatory disease characterized involved the axial joints. The disease could cause arthritis symptom of humpback and extra articular symptoms of osteoporosis and tumors and the patients will lose labor ability under the serious condition. In addition to Diagnostic imaging, increasing studies reported that the occurrence of AS was influenced by genetic and environmental factors, which results from the combined effects of them. Between them, genetic factors are more related with AS. Previous studies suggested that genetic polymorphisms were correlated with AS susceptibility. However, there are no reports about the relationship of HRH4 polymorphisms with AS susceptibility. So our study aimed to explore the association between HRH4 polymorphisms with AS susceptibility.Methods:(1)116 AS patients and 130 healthy individual were selected from Chinese PLA general hospital. Then the case-control study was conducted. The diagnosis of AS was according to the New York criteria amended in 1984. HRH4 polymorphisms were tested by PCR-direct sequencing. Odds ratio (OR),95% confidence interval (CI) and Hardy Weinberg Equilibrium (HWE) of control group calculated by x2 test, were used to evaluate the relationship of HRH4 polymorphisms with AS risk. (2) 50 AS patients and 50 healthy individual were selected from Chinese PLA general hospital. The mRNA expressions of mononuclear cell HRH4 in blood were tested by RT-PCR. Western blot was used to test the expression of HRH4 protein of all subjects. T test was adopted to evaluate the differences on expressions of HRH4 between groups. (3) 20 AS patients,20 Osteoarthritis patients and 20 healthy individual were selected, Real-time quantitative PCR was used to test the mRNA expressions of HRH4 in knee synovial fluid. T test was adopted to evaluate the differences on expressions of HRH4 between three groups.Results:(1) The genotype and allele of HRH4 were related to susceptibility to AS. rs657132 AA genotype increased the risk of AS by 2.767 times (P=0.040, OR=2.667, 95% CI=1.021-6.962). Rs657132 AA genotype may be an important individual susceptible factor in the occurrence and progression of AS. (2) The mRNA expressions of mononuclear cell HRH4 in blood from AS group was obvious higher than healthy control group and the differences were statistical significant (P<0.05). (3) The mRNA expressions of HRH4 in knee synovial fluid significantly increased compared to normal control group.Conclusions:1. HRH4 rs657132 polymorphism was closely related with the occurrence of AS in Chinese Han population.2. The expression of HRH4 increased in AS inflammatory cells, HRH4 may be involved in inflammation.3. The expression of HRH4 in knee synovial fluid from AS patients increased, HRH4 may be an important factor in the occurrence and progression of AS.