Genetic variation in the nuclear factor kappa B pathway in relation to susceptibility to rheumatoid arthritis
ANNALS OF THE RHEUMATIC DISEASES
Authors: Dieguez-Gonzalez, R.; Akar, S.; Calaza, M.; Perez-Pampin, E.; Costas, J.; Torres, M.; Vicario, J. L.; Velloso, M. L.; Navarro, F.; Narvaez, J.; Joven, B.; Herrero-Beaumont, G.; Gonzalez-Alvaro, I.; Fernandez-Gutierrez, B.; de la Serna, A. R.; Carreno, L.; Lopez-Longo, J.; Caliz, R.; Collado-Escobar, M. D.; Blanco, F. J.; Fernandez-Lopez, C.; Balsa, A.; Pascual-Salcedo, D.; Gomez-Reino, J. J.; Gonzalez, A.
Abstract
Objective: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappa B pathway, the major intracellular pathway in RA pathogenesis. Methods: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms ( SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. Results: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. Conclusion: We did not find any major effect among the explored members of the NF-kappa B pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.
Association of chromosome 19 to lung cancer genotypes and phenotypes
CANCER AND METASTASIS REVIEWS
Authors: Wang, Xiangdong; Zhang, Yong; Nilsson, Carol L.; Berven, Frode S.; Andren, Per E.; Carlsohn, Elisabet; Horvatovich, Peter; Malm, Johan; Fuentes, Manuel; Vegvari, Akos; Welinder, Charlotte; Fehniger, Thomas E.; Rezeli, Melinda; Edula, Goutham; Hober, Sophia; Nishimura, Toshihide; Marko-Varga, Gyorgy
Abstract
The Chromosome 19 Consortium, a part of the Chromosome-Centric Human Proteome Project (C-HPP, ), is tasked with the understanding chromosome 19 functions at the gene and protein levels, as well as their roles in lung oncogenesis. Comparative genomic hybridization (CGH) studies revealed chromosome aberration in lung cancer subtypes, including ADC, SCC, LCC, and SCLC. The most common abnormality is 19p loss and 19q gain. Sixty-four aberrant genes identified in previous genomic studies and their encoded protein functions were further validated in the neXtProt database (). Among those, the loss of tumor suppressor genes STK11, MUM1, KISS1R (19p13.3), and BRG1 (19p13.13) is associated with lung oncogenesis or remote metastasis. Gene aberrations include translocation t(15, 19) (q13, p13.1) fusion oncogene BRD4-NUT, DNA repair genes (ERCC1, ERCC2, XRCC1), TGF beta 1 pathway activation genes (TGFB1, LTBP4), Dyrk1B, and potential oncogenesis protector genes such as NFkB pathway inhibition genes (NFKBIB, PPP1R13L) and EGLN2. In conclusion, neXtProt is an effective resource for the validation of gene aberrations identified in genomic studies. It promises to enhance our understanding of lung cancer oncogenesis.
COA
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