Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort

被引：16

作者：

Hellquist, Anna ^{[1
]}

Sandling, Johanna K. ^{[2
]}

Zucchelli, Marco ^{[1
]}

Koskenmies, Sari ^{[3
,4
,5
]}

Julkunen, Heikki ^{[6
]}

D'Amato, Mauro ^{[1
]}

Garnier, Sophie ^{[2
]}

Syvanen, Ann-Christine ^{[2
]}

Kere, Juha ^{[1
,3
,4
]}

机构：

[1] Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden

[2] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[3] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[4] Folkhalsan Inst Genet, Helsinki, Finland

[5] Univ Helsinki, Cent Hosp, Dept Dermatol, FIN-00170 Helsinki, Finland

[6] Univ Helsinki, Cent Hosp, Peijas Hosp, Dept Rheumatol, Vantaa, Finland

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2010年 / 69卷 / 05期

基金：

芬兰科学院; 瑞典研究理事会;

关键词：

RHEUMATOID-ARTHRITIS; RISK; VARIANTS; ITGAM; GENES; SLE; PXK;

D O I：

10.1136/ard.2009.112284

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives To investigate whether 10 single nucleotide polymorphisms (SNPs) and haplotypes in the STAT4 gene, previously associated with systemic lupus erythematosus (SLE) in a Swedish case-control cohort, are also associated with SLE risk in a Finnish SLE family cohort. Method Genotyping was performed in 192 Finnish families, with 237 affected subjects and their healthy relatives, using the SNPstream genotyping system. Results Transmission disequilibrium test analysis provided the strongest signal of association for two linked SNPs: rs7582694 (p=0.002, OR=2.57) and rs10181656 (p=0.001, OR=2.53). Haplotype association analysis using a sliding window approach was also performed and showed that the strongest association signal originates from SNPs in intron 3 of STAT4. Conclusion The main association signal for STAT4 with SLE previously reported in Caucasians is the same in the Finnish population. This is the first study that confirms the association of STAT4 with SLE in a family cohort.

引用

页码：883 / 886

页数：4

共 15 条

[1] STAT4 associates with systemic lupus erythematosus through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk [J].

Abelson, A-K ;

Delgado-Vega, A. M. ;

Kozyrev, S. V. ;

Sanchez, E. ;

Velazquez-Cruz, R. ;

Eriksson, N. ;

Wojcik, J. ;

Reddy, M. V. P. Linga ;

Lima, G. ;

D'Alfonso, S. ;

Migliaresi, S. ;

Baca, V. ;

Orozco, L. ;

Witte, T. ;

Ortego-Centeno, N. ;

Abderrahim, H. ;

Pons-Estel, B. A. ;

Gutierrez, C. ;

Suarez, A. ;

Gonzalez-Escribano, M. F. ;

Martin, J. ;

Alarcon-Riquelme, M. E. .

ANNALS OF THE RHEUMATIC DISEASES, 2009, 68 (11) :1746-1753

[2] Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data [J].

Dudbridge, Frank .

HUMAN HEREDITY, 2008, 66 (02) :87-98

[3] Recruitment of Stat4 to the human interferon-α/β receptor requires activated Stat2 [J].

Farrar, JD ;

Smith, JD ;

Murphy, TL ;

Murphy, KM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) :2693-2697

[4] Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci [J].

Harley, John B. ;

Alarcon-Riquelme, Marta E. ;

Criswell, Lindsey A. ;

Jacob, Chaim O. ;

Kimberly, Robert P. ;

Moser, Kathy L. ;

Tsao, Betty P. ;

Vyse, Timothy J. ;

Langefeld, Carl D. .

NATURE GENETICS, 2008, 40 (02) :204-210

[5] Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX [J].

Hom, Geoffrey ;

Graham, Robert R. ;

Modrek, Barmak ;

Taylor, Kimberly E. ;

Ortmann, Ward ;

Garnier, Sophie ;

Lee, Annette T. ;

Chung, Sharon A. ;

Ferreira, Ricardo C. ;

Pant, P. V. Krishna ;

Ballinger, Dennis G. ;

Kosoy, Roman ;

Demirci, F. Yesim ;

Kamboh, M. Ilyas ;

Kao, Amy H. ;

Tian, Chao ;

Gunnarsson, Iva ;

Bengtsson, Anders A. ;

Rantapaa-Dahlqvist, Solbritt ;

Petri, Michelle ;

Manzi, Susan ;

Seldin, Michael F. ;

Ronnblom, Lars ;

Syvanen, Ann-Christine ;

Criswell, Lindsey A. ;

Gregersen, Peter K. ;

Behrens, Timothy W. .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (09) :900-909

[6] STAT4 - A critical regulator of inflammation in vivo [J].

Kaplan, MH .

IMMUNOLOGIC RESEARCH, 2005, 31 (03) :231-241

[7]

Koskenmies S, 2001, J RHEUMATOL, V28, P758

[8] STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians [J].

Palomino-Morales, R. J. ;

Rojas-Villarraga, A. ;

Gonzalez, C. I. ;

Ramirez, G. ;

Anaya, J-M ;

Martin, J. .

GENES AND IMMUNITY, 2008, 9 (04) :379-382

[9] STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus [J].

Remmers, Elaine F. ;

Plenge, Robert M. ;

Lee, Annette T. ;

Graham, Robert R. ;

Hom, Geoffrey ;

Behrens, Timothy W. ;

de Bakker, Paul I. W. ;

Le, Julie M. ;

Lee, Hye-Soon ;

Batliwalla, Franak ;

Li, Wentian ;

Masters, Seth L. ;

Booty, Matthew G. ;

Carulli, John P. ;

Padyukov, Leonid ;

Alfredsson, Lars ;

Klareskog, Lars ;

Chen, Wei V. ;

Amos, Christopher I. ;

Criswell, Lindsey A. ;

Seldin, Michael F. ;

Kastner, Daniel L. ;

Gregersen, Peter K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (10) :977-986

[10] The innate immune system in SLE:: type I interferons and dendritic cells [J].

Roennblom, L. ;

Pascual, V. .

LUPUS, 2008, 17 (05) :394-399

← 1 2 →