PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus

被引：85

作者：

Tsao, BP ^{[1
]}

Cantor, RM

Grossman, JM

Shen, N

Teophilov, NT

Wallace, DJ

Arnett, FC

Hartung, K

Goldstein, R

Kalunian, KC

Hahn, BH

Rotter, JI

机构：

[1] Univ Calif Los Angeles, Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[4] Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Dept Med, Div Med Genet, Los Angeles, CA 90048 USA

[5] Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Dept Pediat, Div Med Genet, Los Angeles, CA 90048 USA

[6] Cedars Sinai Med Ctr, Dept Rheumatol & Arthrit Dis, Los Angeles, CA 90048 USA

[7] Univ Texas, Hlth Sci Ctr, Dept Internal Med, Div Rheumatol, Houston, TX 77030 USA

[8] Zentralkrankenhaus Reinkenheide, Inst Lab & Transfus Med, D-27574 Bremerhaven, Germany

[9] Univ Ottawa, Ottawa Hosp, Div Rheumatol, Ottawa, ON K1H 8L6, Canada

[10] Univ Calif Los Angeles, Dreyfuss Lab Lupus Res, Los Angeles, CA USA

[11] Cedars Sinai Res Inst, Bertram A Maltz MD Lab Mol Rheumatol, Los Angeles, CA USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1999年 / 103卷 / 08期

关键词：

D O I：

10.1172/JCI5967

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41-q42 region linked to SLE.

引用

页码：1135 / 1140

页数：6

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