The Molecule Epidemiology Study Of Rheumatoid Arthritis And Ankylosing Spondylitis In Chinese Population

Research BackgroundAutoimmune disease (AID) was listed by the World Health Organization as thethird human killer afterCardiovascular disease and cancer in1999. In the same time,autoimmune disease was included as one of ten diseases in the Chinese governmentLong-term Science and Technology Development Program.Due to etiology of AID was not clear, AID has high prevalence, high mortalityand high cost of treatment. Epidemiology is a powerful weapon for human tounderstand etiology of disease.Epidemiology of rheumatic diseases in China juststarted in recent years. There were such many differences of clinical feature betweenChina and developed countries, it‘s important to obtain epidemiology data ofautoimmune disease in China.According to modern medicine, environmental and genetic factors are keys tounderstand etiology of AID. There is interaction between environment and geneticbackground which may be the main risk factor for complex disease such as malignanttumor, AID, metabolic diseases. This study is aimed to explore influence ofenvironment and genetic factor to AID and health people.The study contains two parts: the first section is going to discuss the role ofsmoking and shared epitope (SE) in the pathogenesis of rheumatoid arthritis (RA) andwhether there is an interaction between smoking and SE. The epidemiology data fromEurope shows that there was an interaction between smoking and SE which cansignificantly increases the positivity of anti–cyclic citrullinated peptide (CCP)antibodies. This result suggested that the pathogenesis of anti-CCP antibodies positiveand negative RA were different and directed the way for the following genetic study.However, there were controversy results between different ethnicities. Data fromJapan and south Korean didn‘t show any association between SE and anti-CCPantibodies. China has the largest population especially the largest aging population inthe world, so there was potential largest number of RA patients in China. With thehelp of exploring the association between smoking, SE and RA, we will understandthe pathogenesis and signal way of RA better. The second section is aimed to discussthe prevalence of HLA-B27in Chinese health people and the differences betweendifferent age group. HLA-B27was first reported in1973to be associated withankylosing spondylitis (AS). From that time HLA-B27had been important geneticmarkers to help diagnosis AS. AS is an common AID in China with prevalence of 0.22%. Data from China and other regions showed that positivity of HLA-B27in ASpatients was about85～90%while in healthy people was5～10%, these datasuggested that HLA-B27was an essential gene for AS. Beside AS, HLA-B27wasassociated with many disease such as valvular heart disease, cardiac conduction systemfunction disorders, immune system disorders and certain infectious diseases. So far, there wasnot data of prevalence of HLA-B27in large samples in Chinese.Monitoring the prevalence ofHLA-B27can help national health officials to make decisions to prevention and cure AS andother relevant diseases.Section1:The association study of smoking and Chinese Han patients withRheumatoid Arthritis.1. Objective1.1. To examine the association of smoking and Chinese Han patients withRheumatoid Arthritis.1.2. To examinethe association of smoking, SE and their interaction with RA‘sclinical features.2. Method2.1. Study populationWe collected718RA cases and404healthy donors‘serum and blood. Patientsand controls were reviewed to collectdemography information, smokinghistory.Patients charts were reviewed to collected X-rays (hands only) and clinicalinformation for disease activity score-28(DAS-28).2.2Study method2.2.1Sequence-specific primer polymerase chain reaction (SSP-PCR) was usedto test HLA-DRB1alleles.2.2.2Anti-CCP2assay was used to test anti-CCP antibodies, rheumatoid factor(IgM-RF).2.2.3Sharp score was used to calculate joint invasion2.2.4DAS-28score was used to calculate disease activity.2.2.5Chi-square test was used to calculate the association between smoking andRA. Logistic regression analysis was used to calculate the associationbetween smoking, SE and clinical features of RA.3. Results3.1There was no association of smokingwith RA (p=0.52), anti-CCP positive RA(p=0.58) and RF positive RA (p=0.39). 3.2Interaction between smoking and SE was not associated with RA (p=0.37),anti-CCP positive RA (p=0.50)and RF positive RA (p=0.26).3.3Smoking was not associated with titers of anti-CCP antibodies (p=0.73) andRF (p=0.052), sharp score of joint erosion (p=0.056), the annual rate of jointerosion (p=0.27), DAS28score (p=0.40) and age of disease onset (p=0.32).4. ConclusionSmoking was neither a risk factor for Chinese patients with RA nor a risk factorfor anti-CCP antibodies. Interaction between smoking and SE was not associated withRA, anti-CCP antibody and RFSection2: Investigation of prevalence of HLA-B27in Chinese Hanpopulation of different age group.1. ObjectiveTo investigate of prevalence of HLA-B27in Chinese Han population of differentage group.2. Method2.1Study population3068healthy people from physical examination center of Changzheng Hospitaland Peking University First Hospital were included in our study.2.2Study method2.2.1Sequence-specific primer polymerase chain reaction (SSP-PCR) was usedto test HLA-B27allele.2.2.2Chi-square test was used to calculate the difference between different age,sex andbirthplace groups.2.2.395old (>60years) and2753younger (<60years) Chinese healthy people‘speripheral blood was performed on Illumina iScan system to find snp thatprevalence decline among old people and may have interaction withHLA-B27. According to HAPMAP database we design117taqsnps of13AS related non-MHC gene and200old people‘s peripheral blood wasperformed on Sequenom iPlex platform to test these117snps.2.2.4529old (>60years) and2539younger (<60years) Chinese healthypeople‘s peripheral blood was performed on Sequenom iPlex platform totest snp which was found in step3.3. ResultsTotal prevalence of HLA-B27was5.35%(4.55-6.14) in our study. In the old age group (≥60years) the prevalence was3.55%(2.06-5.05) which was significant lowerthan other group [p=0.031, or=0.6(0.38-0.96)]. There was no difference betweenpeople born in south China and people born in north China (p=0.059). There was nosex differences of HLA-B27.4. ConclusionOur study reveals the approximate distribution of HLA-B27prevalence inChinese. The prevalence was lower in old age group (≥60years), suggesting thatHLA-B27may reduce the life expectancy of carriers. According to the small sizegwas study, SEC16B gene may have interaction with HLA-B27. This conclution needmore study to confirm it.