title: The interferon-gamma receptor gene polymorphisms (Val14Met and Gln64Arg) are not associated with systemic lupus erythematosus in Chinese patients.
abstract: Genetic polymorphism is a difference in DNA sequence among individuals, groups, or populations that give rise to different forms. Differences in DNA sequences that occur naturally in a population. Single nucleotide substitutions, insertions and deletions of nucleotides and repetitive sequences (microsatellites) are all examples of polymorphism. The position at which such a sequence difference is found is a polymorphic site. A single nucleotide substitution is called a single nucleotide polymorphism (SNP). SNPs can occur in coding parts of the gene. If they result in genetic code change, amino-acid polymorphism would occur. The heterodimeric IFN-gamma receptor (IFNGR) complex was made up of two receptor subunits including IFNGR-1 and IFNGR-2. There exist five dbSNP alleles in IFNGR1 exon region and six dbSNP alleles in IFNGR2. Some researchers had found that the greatest risk of the development of systemic lupus erythematosus (SLE) be detected in the individuals who had the Met14/Val14 genotype or the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype in Japanese patients. So we aimed to assess the association between two polymorphisms within the IFNGR gene (A88G and A839G) and SLE in Chinese patients. This study included 154 patients with SLE and 159 unrelated healthy controls. We examined the IFNGR genotype by the reverse transcription-polymerase chain reaction (RT-PCR)-single-strand conformation polymorphism method, RT-PCR-restriction fragment length polymorphism method and DNA sequencing. Genotype frequencies between SLE patients and controls were compared and relationship between genotype frequencies and clinical manifestations of SLE were evaluated. We found that IFNGR2 Arg64/Arg64 genotype decrease the risk of SLE (OR = 2.326, 95% CI 1.181-4.581, Fisher P = 0.015), and the same as IFNGR2 Arg64/Arg64 genotype and IFNGR1 Val14/Val14 genotype combination (OR = 2.420, 95% CI 1.206-4.854, Fisher P = 0.013). The allelic frequency of Val14/Met14 is significantly higher in the patients with oral ulcer or thrombocytopenia when compared with patient without these clinical feature (OR = 4.630, 95% CI 1.370-15.640, Fisher P = 0.021; or OR = 6.368, 95% CI 2.009-20.191, Fisher P = 0.003). On the contrary, the allelic frequency of Val14/Val14 is lower in the patients with oral ulcer or thrombocytopenia than those without these clinical feature (OR = 0.216, 95% CI 0.064-0.730, Fisher P = 0.021; or OR = 0.157, 95% CI 0.050-0.498, Fisher P = 0.003). And after data analysis, we also find that the allelic frequency of Gln64/Gln64 is lower in the patients with arthritis when compared with patient without arthritis (OR = 0.369, 95% CI 0.166-0.818, Fisher P = 0.017). We can conclude that the IFNGR polymorphisms (Val14Met and Gln64Arg) are protective in SLE in Chinese patients. We describe a novel association between Val14/Met14 carriage and patients with oral ulcer or thrombocytopenia.
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Science, Peking Union Medical College, 14 Jiangwangmiao street, Nanjing , 210042, People's Republic of China. dryao_xu@126.com
authors.forename: Xu
authors.initials: X
authors.lastname: Yao
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chen
authors.forename: Juan-Qin
authors.initials: JQ
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017471:Receptors, Interferon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096743:Interferon gamma Receptor
chemical_list: D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C086185:IFNGR2 protein, human