Association of genetic variants of xenobiotic metabolic pathway with systemic lupus erythematosus
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Title |
Association of genetic variants of xenobiotic metabolic pathway with systemic lupus erythematosus
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Creator |
Rupasree, Yedluri
Naushad, Shaik Mohammad Rajasekhar, Liza Kutala, Vijay Kumar |
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Subject |
Systemic lupus erythematosus
Cytochrome P450 1A1 Catecholamine-O-methyl transferase Glutathione-S-transferase Genetic variant Polymorphism Xenobiotic metabolic pathway |
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Description |
447-452
In view of documented evidence that catechol estrogen-DNA adducts serve as epitopes for binding of anti-nuclear antibodies, genetic polymorphisms of the xenobiotic metabolic pathway involved in estrogen metabolism might contribute towards pathophysiology of systemic lupus erythematosus (SLE). To test this hypothesis, a case-control study was conducted. Cytochrome P 450 1A1 (CYP1A1) m4 (OR: 4.93, 95% CI: 1.31-18.49), catecholamine-o-methyl transferase (COMT) H108L (OR: 1.39, 95% CI: 1.03-1.88) and glutathione-S-transferase (GST) T1 null (OR: 1.83, 95% CI: 1.11- 3.01) variants showed association with SLE risk. SHEsis web-based platform analysis showed mild to moderate linkage disequilibrium between the CYP1A1 m1, m2 and m4 variants (D’: 0.19-0.37). Among the different haplotypes of CYP1A1, CAC-haplotype harboring CYP1A1 m1 variant showed association with SLE risk (OR: 1.46, 95% CI: 1.11-1.92). Multifactor dimensionality reduction analysis (MDR) showed potential gene-gene interactions between the phase II variants i.e. COMT H108L × GSTT1 null × GSTM1 null (p<0.0001) and also between the phase II and I variants i.e. COMT H108L × GSTT1 null × CYP1A1 m1 × CYP1A1 m2 in inflating the risk of SLE by 3.33-folds (95% CI: 2.30-4.82) and 4.00-folds (95% CI: 2.77-5.78), respectively. To conclude, hyperinducibility of CYP1A1 due to m1 and m4 variants and defective phase-II detoxification due to COMT H108L and GSTT1 null variants increase the susceptibility to SLE. |
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Date |
2013-10-26T09:49:51Z
2013-10-26T09:49:51Z 2013-10 |
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Type |
Article
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Identifier |
0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/22642 |
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Language |
en_US
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Rights |
CC Attribution-Noncommercial-No Derivative Works 2.5 India
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Publisher |
NISCAIR-CSIR, India
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Source |
IJBB Vol.50(5) [October 2013]
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