Browsing by Subject "Case-Control Studies"

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Open Access
Evaluation of X chromosome inactivation with respect to HLA genetic susceptibility in rheumatoid arthritis and systemic sclerosis
(Public Library of Science, 2016) Kanaan, S. B.; Onat, O. E.; Balandraud, N.; Martin, G. V.; Nelson, J. L.; Azzouz, D. F.; Auger, I.; Arnoux, F.; Martin, M.; Roudier, J.; Ozcelik, T.; Lambert, N. C.
Background: Autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are characterized by a strong genetic susceptibility from the Human Leucocyte Antigen (HLA) locus. Additionally, disorders of epigenetic processes, in particular non-random X chromosome inactivation (XCI), have been reported in many female-predominant autoimmune diseases. Here we test the hypothesis that women with RA or SSc who are strongly genetically predisposed are less susceptible to XCI bias. Methods: Using methylation sensitive genotyping of the androgen receptor (AR) gene, XCI profiles were performed in peripheral blood mononuclear cells from 161 women with RA, 96 women with SSc and 100 healthy women. HLA-DRB1 and DQB1 were genotyped. Presence of specific autoantibodies was documented for patients. XCI skewing was defined as having a ratio ≥ 80:20 of cells inactivating the same X chromosome. Results: 110 women with RA, 68 women with SSc, and 69 controls were informative for the AR polymorphism. Among them 40.9% of RA patients and 36.8% of SSc patients had skewed XCI compared to 17.4% of healthy women (P = 0.002 and 0.018, respectively). Presence of RA-susceptibility alleles coding for the "shared epitope" correlated with higher skewing among RA patients (P = 0.002) and such correlation was not observed in other women, healthy or with SSc. Presence of SSc-susceptibility alleles did not correlate with XCI patterns among SSc patients. Conclusion: Data demonstrate XCI skewing in both RA and SSc compared to healthy women. Unexpectedly, skewed XCI occurs more often in women with RA carrying the shared epitope, which usually reflects severe disease. This reinforces the view that loss of mosaicism in peripheral blood may be a consequence of chronic autoimmunity. © 2016 Kanaan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Open Access
Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritis
(John Wiley & Sons, Inc., 2009) Uz, E.; Mustafa, C.; Topaloglu, R.; Bilginer, Y.; Dursun, A.; Kasapcopur, O.; Ozen, S.; Bakkaloglu, A.; Ozcelik, T.
Objective. Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease of unknown etiology. Two subgroups of JIA, i.e., oligoarticular and polyarticular, are thought to have an autoimmune component, and show a higher female:male ratio. Skewed X chromosome inactivation (XCI) has previously been shown to be associated with scleroderma and autoimmune thyroiditis, 2 autoimmune disorders occurring predominantly in females. This study was undertaken to extend the analysis to the pediatric age group and to determine the XCI profiles of patients with JIA.
Open Access
Lack of association between RNASEL Arg462Gln variant and the risk of breast cancer
(International Institute of Anticancer Research, 2004) Sevinç, A.; Yannoukakos, D.; Konstantopoulou, I.; Manguoglu, E.; Lüleci, G.; Çolak, T.; Akyerli, C.; Çolakoglu, G.; Tez, M.; Sayek, I.; Gerassimos, V.; Nasioulas, G.; Papadopoulou, E.; Florentin, L.; Kontogianni, E.; Bozkurt, B.; Kocabas, N. A.; Karakaya, A. E.; Yulug, I. G.; Özçelik, T.
Background: The RNASEL G1385A variant was recently found to be implicated in the development of prostate cancer. Considering the function of RNase L and the pleiotropic effects of mutations associated with cancer, we sought to investigate whether the RNASEL G1385A variant is a risk factor for breast cancer. Patients and Methods: A total of 453 breast cancer patients and 382 age- and sex-matched controls from Greece and Turkey were analyzed. Genotyping for the RNASEL G1385A variant was performed using an Amplification Refractory Mutation System (ARMS). Results: Statistical evaluation of the RNASEL G1385A genotype distribution among breast cancer patients and controls revealed no significant association between the presence of the risk genotype and the occurrence of breast cancer. Conclusion: Although an increasing number of studies report an association between the RNASEL G1385A variant and prostate cancer risk, this variant does not appear to be implicated in the development of breast cancer.