RGD Reference Report - Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study. - Rat Genome Database

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Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study.

Authors: Horiuchi, T  Washio, M  Kiyohara, C  Tsukamoto, H  Tada, Y  Asami, T  Ide, S  Kobashi, G  Takahashi, H  Takahashi, Hiroki 
Citation: Horiuchi T, etal., Rheumatology (Oxford). 2009 Sep;48(9):1045-9. Epub 2009 Jun 26.
RGD ID: 5147672
Pubmed: PMID:19561157   (View Abstract at PubMed)
DOI: DOI:10.1093/rheumatology/kep166   (Journal Full-text)

OBJECTIVES: Association of the polymorphisms of the genes, TNF receptor type II gene (TNF-RII), cytochrome P4501A1 gene (CYP1A1) and glutathione S-transferase M1 gene (GSTM1), with SLE was investigated. TNF-RII mediates inflammatory and immune response, whereas CYP1A1 and GSTM1 are involved in the metabolism of xenobiotics. These three genes are involved in the generation of reactive oxygen species (ROS), which play a critical role for autoimmune diseases. METHODS: A total of 152 SLE patients and 427 healthy individuals in a female Japanese population were enrolled in the study. Case-control studies were performed for the polymorphisms of these three genes. RESULTS: The carriers of TNF-RII 196R were at a significantly increased risk for SLE with odds ratio (OR) of 1.59 (95% CI = 1.01, 2.52). CYP1A1 3801C homozygotes had a significantly increased risk of SLE (OR = 2.47, 95% CI = 1.28, 4.78). On the other hand, GSTM1 null genotype was not associated with SLE risk. As for combination action of two loci, CYP1A1 3801C/GSTM1 null combination was more strongly associated with an increased risk of SLE (OR = 4.35; 95% CI = 1.76, 10.73). Moreover, TNF-RII 196M/CYP1A1 3801C/GSTM1 null genotype combination was most significantly associated with SLE (OR = 5.83; 95% CI = 2, 17.04). CONCLUSIONS: The individuals carrying two or more 'at-risk' genotypes of TNF-RII, CYP1A1 and GSTM1 had a significantly more increased risk for SLE compared with those having each 'at-risk' genotype. Combination of the risk genotypes will be important to more clearly identify the population at risk for SLE.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP1A1Humansystemic lupus erythematosus susceptibilityIAGP DNA:polymorphism:3' utr:3801T>C (rs4646903)RGD 
Cyp1a1Ratsystemic lupus erythematosus susceptibilityISOCYP1A1 (Homo sapiens)DNA:polymorphism:3' utr:3801T>C (rs4646903)RGD 
Cyp1a1Mousesystemic lupus erythematosus susceptibilityISOCYP1A1 (Homo sapiens)DNA:polymorphism:3' utr:3801T>C (rs4646903)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)

Genes (Mus musculus)
Cyp1a1  (cytochrome P450, family 1, subfamily a, polypeptide 1)

Genes (Homo sapiens)
CYP1A1  (cytochrome P450 family 1 subfamily A member 1)


Additional Information