Genetic polymorphisms associated with cigarette smoking and the risk of Graves' disease.
OBJECTIVE
Cigarette smoking is a well-recognized risk factor of Graves' disease and, particularly, Graves' ophthalmopathy. Hence, germline polymorphisms of detoxification genes and genes belonging to the major DNA repair-apoptosis pathways might have an important role in disease susceptibility. In addition, as some of these genes are regulated by thyroid hormones, they may affect the patients' outcomes. We aimed to assess the influence of the GST, CYP and TP53 gene polymorphisms in the risk of Graves' disease and its outcome.


METHODS
Prospective case-control study.


METHODS
A PCR-based strategy was used for GSTT1, GSTM1, GSTP1, CYP1A1 and TP53 codon 72 genotypes in a group of 400 Graves' disease patients, and to compare them to 574 control individuals with similar environmental exposure features.


RESULTS
GSTM1 and GSTT1 genotypes were equally distributed in cases and controls, respectively. However, GSTP1 (P < 0.0001), CYP1A1 (P < 0.0033) and Pro/ProTP53 (P < 0.0035) variants appeared more frequently in Graves' disease patients than in controls. A multivariate analysis indicated that cigarette smoking and inheritance of GSTP1, CYP1A1 and Pro/ProTP53 variants were important risk factors for Graves' disease, but only smoking appeared as an independent risk factor for Graves' ophthalmopathy. There was no association between clinical features, including ophthalmopathy or treatment outcome, and the studied genotypes.


CONCLUSIONS
We concluded that GSTP1, CYP1A1 and TP53, but not GSTT1 and GSTM1 germline polymorphisms, may be associated with smoking-related Graves' disease susceptibility and configure a risk profile for the disease. However, these polymorphisms do not influence the patients' response to treatment.
Bufalo
Natássia E
NE
Molecular Genetics of Cancer Laboratory, Department of Internal Medicine, Medical Science School-FCM, State University of Campinas, Sao Paulo, Brazil.
Santos
Roberto B
RB
Cury
Adriano N
AN
Andrade
Renato A
RA
Morari
Joseane
J
Morari
Elaine C
EC
Leite
Janaína L
JL
Monte
Osmar
O
Romaldini
João H
JH
Ward
Laura S
LS
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006111:Graves Disease / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012907:Smoking / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D016159:Tumor Suppressor Protein p53; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase