Genetic variation in CYP1A1 and AHRR genes increase the risk of systemic lupus erythematosus and exacerbate disease severity in smoker patients.
Adult
Alleles
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Case-Control Studies
Cigarette Smoking
Cytochrome P-450 CYP1A1
/ genetics
Female
Gene-Environment Interaction
Genetic Predisposition to Disease
Genetic Variation
Genotype
Haplotypes
Humans
Lupus Erythematosus, Systemic
/ genetics
Male
Repressor Proteins
/ genetics
Severity of Illness Index
Xenobiotics
/ metabolism
CYP1A1
aryl hydrocarbon receptor
genotyping
systemic lupus erythematosus
xenobiotic
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
18
08
2021
received:
31
12
2020
accepted:
01
09
2021
pubmed:
29
9
2021
medline:
15
2
2022
entrez:
28
9
2021
Statut:
ppublish
Résumé
Genetic variations of aryl hydrocarbon receptor (AHR) pathway genes could influence the imbalanced immune response to xenobiotics. Therefore, we aimed to investigate the polymorphism of AHR pathway genes in systemic lupus erythematosus (SLE) patients in association with smoking. Genomic DNA from patients (N = 107) and controls (N = 105) of a population from northeast of Iran was used for genotyping of CYP1A1 T>C (rs4646903) and AHRR C>G (rs2292596) variants. The SLEDAI score and smoking status of the patients were registered. The AHR activity was estimated by CYP1A1 and CYP1B1 gene expression in peripheral blood mononuclear cells (PBMC). The C allele in rs4646903 (odds ratio [OR] = 2.67) and G allele in rs2292596 (OR = 1.79) SNPs were significantly associated with the increased risk of SLE. The AHR pathway was more active in high-risk CYP1A1/AHRR: C/G haplotype. The most severe disease was observed in smoker patients with high-risk haplotype and both smoking (Exp (β) = 9.5) and high-risk CYP1A1/AHRR (C/G) haplotype (Exp (β) = 3.7) can significantly increase the likelihood of having severe (SLEDAI ≥ 20) SLE disease activity. Our findings indicated the association of xenobiotic-metabolizing genes (CYP1A1, AHRR) polymorphisms with the susceptibility to SLE and disease severity regarding the smoking background, suggesting the interaction of gene and environmental risk factors in SLE pathogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic variations of aryl hydrocarbon receptor (AHR) pathway genes could influence the imbalanced immune response to xenobiotics. Therefore, we aimed to investigate the polymorphism of AHR pathway genes in systemic lupus erythematosus (SLE) patients in association with smoking.
METHODS
METHODS
Genomic DNA from patients (N = 107) and controls (N = 105) of a population from northeast of Iran was used for genotyping of CYP1A1 T>C (rs4646903) and AHRR C>G (rs2292596) variants. The SLEDAI score and smoking status of the patients were registered. The AHR activity was estimated by CYP1A1 and CYP1B1 gene expression in peripheral blood mononuclear cells (PBMC).
RESULTS
RESULTS
The C allele in rs4646903 (odds ratio [OR] = 2.67) and G allele in rs2292596 (OR = 1.79) SNPs were significantly associated with the increased risk of SLE. The AHR pathway was more active in high-risk CYP1A1/AHRR: C/G haplotype. The most severe disease was observed in smoker patients with high-risk haplotype and both smoking (Exp (β) = 9.5) and high-risk CYP1A1/AHRR (C/G) haplotype (Exp (β) = 3.7) can significantly increase the likelihood of having severe (SLEDAI ≥ 20) SLE disease activity.
CONCLUSION
CONCLUSIONS
Our findings indicated the association of xenobiotic-metabolizing genes (CYP1A1, AHRR) polymorphisms with the susceptibility to SLE and disease severity regarding the smoking background, suggesting the interaction of gene and environmental risk factors in SLE pathogenesis.
Substances chimiques
AHRR protein, human
0
Basic Helix-Loop-Helix Transcription Factors
0
Repressor Proteins
0
Xenobiotics
0
CYP1A1 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1A1
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22916Subventions
Organisme : Golestan University of Medical Sciences
ID : 970710119
Informations de copyright
© 2021 Wiley Periodicals LLC.
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