OBJECTIVE: The development and severity of Graves' ophthalmopathy (GO) may result from a complex interplay of genetic and environmental factors. The aim of this study was to investigate the association of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and non-genetic factors (age, sex, cigarette smoking) with GO in two different populations, Polish-Caucasians and Japanese. DESIGN: We investigated the distribution of CTLA-4 A49G polymorphism in 264 Caucasian patients with Graves' disease (GD), of which 95 had clinically evident GO (NOSPECS class >or=3) and 319 Japanese patients with GD, of which 99 had ophthalmopathy. The control groups consisted of healthy Polish adults (n=194), Polish centenarians (n=51) and Japanese adults (n=112). RESULTS: Allele G and G/G genotype were significantly increased in Caucasian patients with GD (48% and 25% respectively) and in Japanese patients with GD (69% and 47% respectively) compared with control groups. There were no significant differences in the G allele and G/G genotype frequencies in GO patients compared with GD patients without ophthalmopathy. Multiple logistic regression analysis demonstrated that cigarette smoking (P=0.03, odds ratio (OR)=1.7) and age of onset of GD over 42 Years (P=0.08; OR=1.6) were contributing factors associated with susceptibility to GO in Polish patients. In Japanese patients, a younger age of onset of GD had an effect on the development of GO (P=0.02, OR=1.8). CONCLUSIONS: (i) Allele G and G/G genotype confer genetic susceptibility to GD; (ii) CTLA-4 A49G polymorphism is not associated with the development of GO; (iii) different non-genetic factors may contribute to GO in different populations.
OBJECTIVE: The development and severity of Graves' ophthalmopathy (GO) may result from a complex interplay of genetic and environmental factors. The aim of this study was to investigate the association of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and non-genetic factors (age, sex, cigarette smoking) with GO in two different populations, Polish-Caucasians and Japanese. DESIGN: We investigated the distribution of CTLA-4A49G polymorphism in 264 Caucasian patients with Graves' disease (GD), of which 95 had clinically evident GO (NOSPECS class >or=3) and 319 Japanese patients with GD, of which 99 had ophthalmopathy. The control groups consisted of healthy Polish adults (n=194), Polish centenarians (n=51) and Japanese adults (n=112). RESULTS: Allele G and G/G genotype were significantly increased in Caucasian patients with GD (48% and 25% respectively) and in Japanese patients with GD (69% and 47% respectively) compared with control groups. There were no significant differences in the G allele and G/G genotype frequencies in GO patients compared with GDpatients without ophthalmopathy. Multiple logistic regression analysis demonstrated that cigarette smoking (P=0.03, odds ratio (OR)=1.7) and age of onset of GD over 42 Years (P=0.08; OR=1.6) were contributing factors associated with susceptibility to GO in Polish patients. In Japanese patients, a younger age of onset of GD had an effect on the development of GO (P=0.02, OR=1.8). CONCLUSIONS: (i) Allele G and G/G genotype confer genetic susceptibility to GD; (ii) CTLA-4A49G polymorphism is not associated with the development of GO; (iii) different non-genetic factors may contribute to GO in different populations.
Authors: Krystian Jazdzewski; Tomasz Bednarczuk; Magdalena Stepnowska; Sandya Liyanarachchi; Krystyna Suchecka-Rachon; Janusz Limon; Krzysztof Narkiewicz Journal: Int J Mol Med Date: 2007-01 Impact factor: 4.101
Authors: Lee-Shing Chang; Romualdo Barroso-Sousa; Sara M Tolaney; F Stephen Hodi; Ursula B Kaiser; Le Min Journal: Endocr Rev Date: 2019-02-01 Impact factor: 19.871