An association study of 22 candidate genes in psoriasis families reveals shared genetic factors with other autoimmune and skin disorders.
Psoriasis is a common inflammatory and hyperproliferative skin disease. Recent studies have reported that common genetic factors may underlie both skin and immune-mediated disorders. We hypothesized that such genes may be involved in susceptibility to psoriasis, and undertook an association analysis of 22 candidate genes in a set of French high-risk psoriasis families. One hundred fifty-three single-nucleotide polymorphisms (SNPs) were genotyped and the transmission of alleles in nuclear families was analyzed using the FBAT (family-based association test). To further investigate suggestive associations, LNM (logistic-normal models) and MQLS (modified quasi-likelihood score) methods, which take the whole pedigree structure information of families into consideration, were also applied. Our study supported the involvement of six candidate genes in susceptibility to psoriasis: SCL12A8, which belongs to the solute carrier gene family; FLG and TGM5, which are involved in epidermal differentiation; CARD15 and CYLD, which modulate the transcription factor NF-kB; and IL1RN, which encodes an IL receptor antagonist. Furthermore, we found evidence for interaction between the major risk allele, HLA-Cw6, and CARD15, CYLD, and TGM5 susceptibility alleles. Taken together, our data show that shared genetic factors may contribute to the etiology of both psoriasis and other skin or immune-mediated disorders.
Oudot
Tiphaine
T
CEA, Institut de Génomique, Centre National de Génotypage, Evry, France.
Lesueur
Fabienne
F
Guedj
Mickaël
M
de Cid
Rafael
R
McGinn
Steven
S
Heath
Simon
S
Foglio
Mario
M
Prum
Bernard
B
Lathrop
Mark
M
Prud'homme
Jean-François
JF
Fischer
Judith
J
D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics; D030541:Databases, Genetic; D005192:Family Health; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*; D017978:Receptors, Growth Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D002352:Carrier Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D015236:HLA-C Antigens; D017978:Receptors, Growth Factor; D014157:Transcription Factors