The Missense Variation Q705K in CIAS1/NALP3/NLRP3 Gene and an NLRP1 Haplotype Are Associated With Celiac Disease

被引：86

作者：

Pontillo, Alessandra ^{[1
]}

Vendramin, Anna ^{[1
]}

Catamo, Eulalia ^{[1
]}

Fabris, Annalisa ^{[1
]}

Crovella, Sergio ^{[1
,2
]}

机构：

[1] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Med Genet Serv, Trieste, Italy

[2] Univ Fed Pernambuco, Dept Genet, Recife, PE, Brazil

来源：

AMERICAN JOURNAL OF GASTROENTEROLOGY | 2011年 / 106卷 / 03期

关键词：

RISK VARIANTS; INFLAMMASOME; CRYOPYRINOPATHIES; IDENTIFICATION; POPULATION; NALP1; CELLS; CIAS1;

D O I：

10.1038/ajg.2010.474

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVES: Celiac disease (CD) is a multifactorial common disorder with several susceptibility loci. Variations in the NALP1/NLRP1 and NALP3/NLRP3 genes have been reported to confer risk for several autoimmune conditions. We hypothesized that polymorphisms in these genes, due to their role in innate immunity and inflammatory processes, may affect susceptibility to CD. METHODS: Two single-nucleotide polymorphisms (SNPs) in NLRP1 (rs12150220, rs2670660) and two SNPs (rs10754558, rs35829419) in NLRP3 genes were genotyped in 504 CD Italian patients and 256 healthy controls. RESULTS: The minor A allele of NLRP3 rs35829419 (Q705K) polymorphism appeared to exert a protective role against the development of CD (P = 0.029; odds ratio (OR) = 0.56). Moreover, a particular NLRP1 haplotype was associated with predisposition to CD (P = 0.003; OR = 1.38), even more when present in combination with the rs35829419 major C allele (P = 0.002; OR = 1.42). CONCLUSIONS: We hypothesized that the deregulation of CIAS1/NALP3/NLRP3 and NALP1/NLRP1 inflammasomes could have a role in CD pathogenesis

引用

页码：539 / 544

页数：6

共 27 条

[1]

The clinical continuum of cryopyrinopathies -: Novel CIAS1 mutations in north American patients and a new cryopyrin model [J].

Aksentijevich, Ivona ;

Putnam, Christopher D. ;

Remmers, Elaine F. ;

Mueller, James L. ;

Le, Julie ;

Kolodner, Richard D. ;

Moak, Zachary ;

Chuang, Michael ;

Austin, Frances ;

Goldbach-Mansky, Raphaela ;

Hoffman, Hal M. ;

Kastner, Daniel L. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (04) :1273-1285

[2]

Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[3]

Rapid genetic screening for major human leukocyte antigen risk haplotypes in patients with type 1 diabetes from Northeastern Brazil [J].

Brandao, Lucas C. ;

Vatta, Serena ;

Guimaraes, Rafael ;

Segat, Ludovica ;

Araujo, Jaqueline ;

De Lima Filho, Jose L. ;

Arraes, Luiz C. ;

Not, Tarcisio ;

Crovella, Sergio .

HUMAN IMMUNOLOGY, 2010, 71 (03) :277-280

[4]

Clinical and genetic characterization of Italian patients affected by CINCA syndrome [J].

Caroli, F. ;

Pontillo, A. ;

D'Osualdo, A. ;

Travan, L. ;

Ceccherini, I. ;

Crovella, S. ;

Alessio, M. ;

Stabile, A. ;

Gattorno, M. ;

Tommasini, A. ;

Martini, A. ;

Lepore, L. .

RHEUMATOLOGY, 2007, 46 (03) :473-478

[5]

Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis [J].

Cox, DG ;

Canzian, F .

BIOINFORMATICS, 2001, 17 (08) :738-739

[6]

Genetics and pathogenesis of coeliac disease [J].

Heap, Graham A. ;

van Heel, David A. .

SEMINARS IN IMMUNOLOGY, 2009, 21 (06) :346-354

[7]

Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma [J].

Hitomi, Yuki ;

Ebisawa, Motohiro ;

Tomikawa, Morimitsu ;

Imai, Takanori ;

Komata, Takatsugu ;

Hirota, Tomomitsu ;

Harada, Michishige ;

Sakashita, Masafumi ;

Suzuki, Yoichi ;

Shimojo, Naoki ;

Kohno, Yoichi ;

Fujita, Kimie ;

Miyatake, Akihiko ;

Doi, Satoru ;

Enomoto, Tadao ;

Taniguchi, Masami ;

Higashi, Noritaka ;

Nakamura, Yusuke ;

Tamari, Mayumi .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 124 (04) :779-785

[8]

Fine structure mapping of CIAS1:: identification of an ancestral haplotype and a common FCAS mutation, L353P [J].

Hoffman, HM ;

Gregory, SG ;

Mueller, JL ;

Tresierras, M ;

Broide, DH ;

Wanderer, AA ;

Kolodner, RD .

HUMAN GENETICS, 2003, 112 (02) :209-216

[9]

Newly identified genetic risk variants for celiac disease related to the immune response [J].

Hunt, Karen A. ;

Zhernakova, Alexandra ;

Turner, Graham ;

Heap, Graham A. R. ;

Franke, Lude ;

Bruinenberg, Marcel ;

Romanos, Jihane ;

Dinesen, Lotte C. ;

Ryan, Anthony W. ;

Panesar, Davinder ;

Gwilliam, Rhian ;

Takeuchi, Fumihiko ;

McLaren, William M. ;

Holmes, Geoffrey K. T. ;

Howdle, Peter D. ;

Walters, Julian R. F. ;

Sanders, David S. ;

Playford, Raymond J. ;

Trynka, Gosia ;

Mulder, Chris J. J. ;

Mearin, M. Luisa ;

Verbeek, Wieke H. M. ;

Trimble, Valerie ;

Stevens, Fiona M. ;

O'Morain, Colm ;

Kennedy, Nicholas P. ;

Kelleher, Dermot ;

Pennington, Daniel J. ;

Strachan, David P. ;

McArdle, Wendy L. ;

Mein, Charles A. ;

Wapenaar, Martin C. ;

Deloukas, Panos ;

McGinnis, Ralph ;

McManus, Ross ;

Wijmenga, Cisca ;

van Heel, David A. .

NATURE GENETICS, 2008, 40 (04) :395-402

[10]

NALP1 in vitiligo-associated multiple autoimmune disease [J].

Jin, Ying ;

Mailloux, Christina M. ;

Gowan, Katherine ;

Riccardi, Sheri L. ;

LaBerge, Greggory ;

Bennett, Dorothy C. ;

Fain, Pamela R. ;

Spritz, Richard A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (12) :1216-1225

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