Genetic susceptibility to Graves' ophthalmopathy: The role of polymorphisms in anti-inflammatory cytokine genes.
BACKGROUND
Various polymorphisms occur in cytokine genes involved in inflammatory processes in Graves' ophthalmopathy (GO). Anti-inflammatory cytokines such as transforming growth factor- β (TGF-β), interleukin-10 (IL-10) and interleukin-4 (IL-4) are among those believed to be involved in the disease process. In this study, we investigated the association between 8 polymorphisms within the mentioned cytokines and GO.


METHODS
The following polymorphisms were studied in 50 patients with GO, 57 Graves' patients without GO and 140 healthy individuals using polymerase chain reaction with sequence-specific primers: TGF-β (+869C/T, +915G/C), IL-10 (-1082A/G, -819C/T, -592C/A) and IL-4 (-1098T/G, -590T/C, -33C/T). A corrected p value less than 0.05 was considered statistically significant.


RESULTS
The TGF-β +915C allele (Odds Ratio [OR] = 2.20) and CC genotype (OR = 7.50) as well as +869C allele (OR = 2.21) showed significant correlations with GO. Regarding IL-4 polymorphisms, the -1098G allele (OR = 2.09) and GG genotype (OR = 7.49), and the -33T allele (OR = 2.05) and TT genotype (OR = 4.00) were significantly associated with GO. The IL-10 -819TT genotype (OR = 5.00) was significantly correlated with GO.


CONCLUSIONS
This is the first study to show that polymorphisms in anti-inflammatory cytokine genes are associated with susceptibility to GO.
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Omid
O
Khalilzadeh
Mehdi
M
Anvari
Alireza
A
Esteghamati
Fatemeh
F
Momen-Heravi
Armin
A
Rashidi
Hoda Mojazi
HM
Amiri
Maryam
M
Tahvildari
Mahdi
M
Mahmoudi
Aliakbar
A
Amirzargar
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D049970:Graves Ophthalmopathy / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016207:Cytokines; D017931:DNA Primers; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4