title: Association of TLR4 gene non-missense single nucleotide polymorphisms with rheumatoid arthritis in Chinese Han population.
abstract: Toll-like receptor4 (TLR4) plays an important role in the induction and regulation of the innate or adaptive immune responses. Thus, the genetic variation in TLR4 gene may influence the development of autoimmune diseases such as rheumatoid arthritis (RA). Several studies have investigated the roles of genetic polymorphisms of TLR4 gene in RA, but most of these studies were restricted to two cosegregating functional missense polymorphisms Asp299Gly and Thr399Ile. To determine whether non-missense genetic polymorphisms located in regulatory region of TLR4 are related to RA in a Chinese Han population, four single nucleotide polymorphisms (SNPs) situated on 3' untranslating region (UTR) and 5' UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques. Significant genetic associations were observed with the 3' UTR SNP rs41426344 and rs7873784. The minor allele C and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784 were identified to be risk factors for the development of RA in Chinese Han people. Furthermore, by comparing the variation allele frequencies to other populations, prevalent genetic ethnic specificity was observed in all the four SNPs. Our study suggested that the effect of non-missense polymorphisms located in regulatory region would not be neglected in disease association analysis.
authors.affiliation: Key Laboratory of Bioresources Conservation and Utilization and Human Genetics Center of Yunnan University, Kunming 650091, Yunnan, People's Republic of China.
authors.forename: Hongju
authors.initials: H
authors.lastname: Yang
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Wei
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Shou
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Chunjie
authors.initials: C
authors.lastname: Xiao
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Zhili
authors.initials: Z
authors.lastname: Yang
authors.forename: Jieying
authors.initials: J
authors.lastname: Zhang
authors.forename: Bingrong
authors.initials: B
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044466:Asian People; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4