@article{f5cc03ef228747ffa2a53a5345a38a21,
title = "Genetic associations of LYN with systemic lupus erythematosus",
abstract = "We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P = 1.1 × 10-4, odds ratio (OR) = 0.81 (95% confidence interval: 0.73 - 0.90)). This single nucleotide polymorphism (SNP) is located in the 5′ untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P = 1.5 × 10-3, OR = 0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.",
author = "R. Lu and Vidal, {G. S.} and Kelly, {J. A.} and Delgado-Vega, {A. M.} and Howard, {X. K.} and Macwana, {S. R.} and N. Dominguez and W. Klein and C. Burrell and Harley, {I. T.} and Kaufman, {K. M.} and Bruner, {G. R.} and Moser, {K. L.} and Gaffney, {P. M.} and Gilkeson, {G. S.} and Wakeland, {E. K.} and Li, {Q. Z.} and Langefeld, {C. D.} and Marion, {M. C.} and J. Divers and Alarc{\'o}n, {G. S.} and Brown, {E. E.} and Kimberly, {R. P.} and Edberg, {J. C.} and R. Ramsey-Goldman and Reveille, {J. D.} and G. McGwin and Vil{\'a}, {L. M.} and Petri, {M. A.} and Bae, {S. C.} and Cho, {S. K.} and Bang, {S. Y.} and I. Kim and Choi, {C. B.} and J. Martin and Vyse, {T. J.} and Merrill, {J. T.} and Harley, {J. B.} and Alarc{\'o}n-Riquelme, {M. E.} and Nath, {S. K.} and James, {J. A.} and Guthridge, {J. M.}",
note = "Funding Information: Members of BIOLUPUS who have provided samples to this study are: Peter Junker, Ann Voss and Helle Laustrup (Odense, Denmark), Bernard Lawerys and Fredric Houssieau (Louvain, Belgium), Carlos Vasconce-los and Berta Martins Da Silva (Porto, Portugal), Carmen Gutierrez and Ana Su{\'a}rez (Oviedo, Spain), Torsten Witte (Hannover, Germany), Sandra D{\textquoteright}Alfonso, Sergio Migliar-esi, Mauro Galeazzi and Gian Domenico Sebastiani (Novara, Naples, Siena and Rome, Italy), Bernardo Pons-Estel and the members of GENLES (Rosario, Argentina) and Emoke Endreffy (Szeged, Hungary). Peter K Gregersen from the Feinstein Institute of Medical Research and Jorge R Oksenberg from the University of California at San Francisco graciously provided controls used in this study. Members of PROFILE who have provided samples to this study are Graciela S Alarc{\'o}n, Elizabeth E Brown, Robert P Kimberly, Jeffery C Edberg and Gerald McGwin, Jr (University of Alabama Birmingham, Birmingham, AL, USA), Rosalind Ramsey-Goldman (Northwestern University Feinberg School of Medicine, Chicago, IL, USA), John D Reveille (University Texas Health Science Center, Houston, TX, USA), Luis M Vil{\'a} (University of Puerto Rico Medical Sciences Cam- pus, San Juan, PR, USA) and Michelle A Petri (Johns Hopkins Hospital, Baltimore, MD, USA). This project was funded by National Institutes of Health RR020143 (JMG and JBH), RR015577 (JMG, JBH, JAJ), NIAID-HHSN266200500026C (JMG and JAJ), AI031584 (JBH, JMG, JAJ), AR053483 (JMG, SKN and JAJ), AR48940 (JBH, JAJ), AI063622 (SKN), Kirkland Scholar awards (JBH and JAJ), AR049084 (SKN, JBH, RPK, RRG, JDR, MAP, LMV, GSA, JCE, GMcG Jr), AR42460 (JBH), AR12253 (JBH), AR62277 (JBH), AI24717 (JBH), AI063274 (PMG), AR052125 (PMG), AR043247 (KLM), DEO15223 (JBH), Alliance for Lupus Research (JBH), the US Department of Veterans Affairs (JBH), Swedish Research Council (MEAR), the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea. (A010252, A080588) (SCB), the Torsten & Ragnar S{\"o}derbergs Foundation (MEAR), the Swedish Foundation Against Rheumatism (MEAR), the Gustaf Vth-80th-Year Foundation (MEAR), Plan Nacional de I + D, Spain (SAF06-00398) (JM), the Junta de Andaluc{\'i}a, grupo CTS-180 (JM) and OHRS award # HR08-037 from the Oklahoma Center for the Advancement of Science & Technology (JMG). Dr Harley has received consulting fees, speaking fees and/or director{\textquoteright}s fees from Bio-Rad Laboratories, Merck, UCB Inc., ImmunoVision Inc., IVAX Diagnostics and JK Autoimmunity and owns stock or stock options in IVAX Diagnostics.",
year = "2009",
doi = "10.1038/gene.2009.19",
language = "English (US)",
volume = "10",
pages = "397--403",
journal = "Genes and immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "5",
}