Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription

Joel M. Guthridge, Rufei Lu, Harry Sun, Celi Sun, Graham B. Wiley, Nicolas Dominguez, Susan R. MacWana, Christopher J. Lessard, Xana Kim-Howard, Beth L. Cobb, Kenneth M. Kaufman, Jennifer A. Kelly, Carl D. Langefeld, Adam J. Adler, Isaac T.W. Harley, Joan T. Merrill, Gary S. Gilkeson, Diane L. Kamen, Timothy B. Niewold, Elizabeth E. BrownJeffery C. Edberg, Michelle A. Petri, Rosalind Ramsey-Goldman, John D. Reveille, Luis M. Vilá, Robert P. Kimberly, Barry I. Freedman, Anne M. Stevens, Susan A. Boackle, Lindsey A. Criswell, Tim J. Vyse, Timothy W. Behrens, Chaim O. Jacob, Marta E. Alarcón-Riquelme, Kathy L. Sivils, Jiyoung Choi, Young Bin Joo, So Young Bang, Hye Soon Lee, Sang Cheol Bae, Nan Shen, Xiaoxia Qian, Betty P. Tsao, R. Hal Scofield, John B. Harley, Carol F. Webb, Edward K. Wakeland, Judith A. James, Swapan K. Nath, Robert R. Graham, Patrick M. Gaffney

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage. Allelic differences at rs1382568 resulted in altered promoter activity in B progenitor cell lines. Thus, our results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses.

Original languageEnglish (US)
Pages (from-to)586-598
Number of pages13
JournalAmerican journal of human genetics
Issue number4
StatePublished - Apr 3 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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