Gender-dependent and age-of-onset-specific association of the rs11675434 single-nucleotide polymorphism near TPO with susceptibility to Graves' ophthalmopathy.
The role of TPO gene polymorphism in the susceptibility to Graves' disease (GD) remains unclear. However, single-nucleotide polymorphisms (SNPs) near TPO have been recently associated with serum levels of thyroid peroxidase (TPO) antibody in two independent genome-wide association studies. Moreover, we have observed a strong association between the rs11675434 SNP located near TPO and the presence of clinically evident Graves' ophthalmopathy (GO). The aim of the current study was to reevaluate and dissect this association in an extended group of 1231 well-characterized patients with GD (1043 adults and 188 children) and 1130 healthy controls from the Polish Caucasian population, considering possible gender-dependent and age-of-onset-specific effects of the studied SNP. We found that the T allele of rs11675434 was significantly more frequent in GD patients with than without GO (odds ratio (OR)=1.26, 95% confidence interval (CI)=1.05-1.51, P=0.012), which was consistent with our previous findings. Further analyses performed in subgroups of patients showed that the association with GO was significant in adult patients with age of GD onset ⩾45 years (OR=1.34, 95% CI=1.03-1.75, P=0.031), but not in children and adolescents or adult patients with earlier onset of the disease (OR=1.72, 95% CI=0.77-3.84, P=0.18 and OR=1.05, 95% CI=0.79-1.40, P=0.75, respectively). Moreover, a strong association with GO was present in males (OR=2.06, 95% CI=1.40-3.02, P=0.0002), whereas it was absent in females (OR=1.10, 95% CI=0.90-1.35, P=0.35). The results of our study further suggest that rs11675434 SNP located near TPO is associated with the development of GO, especially in males and patients with later age of GD onset.
Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
Aleksander
A
Kuś
Department of Medical Genetics, Centre for Biostructure, Medical University of Warsaw, Warsaw, Poland.
Konrad
K
Szymański
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Beata
B
Jurecka-Lubieniecka
Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Edyta
E
Pawlak-Adamska
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Dorota
D
Kula
Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
Piotr
P
Miśkiewicz
Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.
Marek
M
Bolanowski
Department of Medical Genetics, Centre for Biostructure, Medical University of Warsaw, Warsaw, Poland.
Rafał
R
Płoski
Department of Pediatrics, Endocrinology and Diabetes with a Cardiology Unit, Medical University of Bialystok, Bialystok, Poland.
Artur
A
Bossowski
Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.
Jacek
J
Daroszewski
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Barbara
B
Jarząb
Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
Tomasz
T
Bednarczuk
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D002648:Child; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D049970:Graves Ophthalmopathy / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000276:immunology; D008297:Male; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
D001323:Autoantibodies; D007453:Iodide Peroxidase