title: Association analysis of single nucleotide polymorphisms of proinflammatory cytokine and their receptors genes with rheumatoid arthritis in northwest Chinese Han population.
abstract: OBJECTIVE
  To analyze the relationship of genetic polymorphisms in IL1β, IL6, TNF-α genes and their receptors genes with rheumatoid arthritis (RA) for northwest Han Chinese. This study also explores whether there are gene-gene interactions among these genetic polymorphisms.
  
  
  METHODS
  A total of 452 patients with RA and 373 matched healthy controls were enrolled to carry out a case-control study for 16 SNPs of IL1B-511 C>T, IL1B-31 T>C, IL1B+3954 C>T, IL1RN T>C, IL6-597 G>A, IL6-572 G>C, IL6-174 G>C, IL6R-183 G>A, IL6R exon2 T>A, IL6R exon1 A>C, TNFA-863 C>A, TNFA-857 C>T, TNFA-308 G>A, TNFA-238 G>A, TNFR1-383 A>C and TNFR2 T676G T>G from seven genes. Genotyping for the SNPs was conducted on the RotorGene 6000 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to discover likely gene-gene interaction model among the SNPs.
  
  
  RESULTS
  The results showed that the genotype distributions of TNFA-308, TNFA-857 and TNFA-863 are significantly different between case and control groups (P=0.016, P=0.048 and P=0.016, respectively). Carriers of TNFA-857 mutant allele conferred risk to RA (OR=1.525, 95% CI=1.157-2.009) while those of TNFA-308 and TNFA-863 mutant alleles conferred protection to RA (OR=0.459, 95% CI=0.286-0.739; OR=0.490, 95% CI=0.329-0.732). GMDR analysis for the SNPs indicated that gene-gene interaction existed among IL1B-31, IL1RN, IL6-572, IL6R-183, IL6R-exon1 and TNFA-857. Thirteen of all genotypes of the six SNPs combination were discovered to have significant distribution difference between RA group and the control.
  
  
  CONCLUSIONS
  This study demonstrated that PCR-HRM assay is a highly efficient SNP genotyping method especially for the detection of large-scale samples. The SNPs of TNFA-308 and TNFA-863 are closely associated with RA susceptibility and that gene-gene interactions may occur among the six SNPs of IL1B-31, IL1RN, IL6-572, IL6R-183, IL6R-exon1 and TNFA-857 in RA patients from northwest Chinese Han population, especially these SNPs' combination genotypes CT/TT/CC/GG/AC/CC, CT/TT/GC/AA/AC/CT and CT/CT/CC/GA/AC/CC to show high risk of RA susceptibility in our study.
authors.affiliation: Central Laboratory, Gansu Province Key Laboratory of Digestive System Tumors, Lanzhou University Second Hospital, 730030 Lanzhou, China.
authors.forename: Chong-ge
authors.initials: CG
authors.lastname: You
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Yu-min
authors.initials: YM
authors.lastname: Li
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Fei-fei
authors.initials: FF
authors.lastname: Li
authors.forename: Xin-ling
authors.initials: XL
authors.lastname: Guo
authors.forename: Li-na
authors.initials: LN
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha