Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis.
OBJECTIVE
The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA.


METHODS
We tested for association between the LCE3C_LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C_LCE3B deletion (LCE3C_LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package.


RESULTS
An association of homozygosity for the LCE3C_LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C_LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients.


CONCLUSIONS
We have identified an association between the LCE3C_LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C_LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.
Docampo
Elisa
E
Center for Genomic Regulation-Pompeu Fabra University and Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain.
Rabionet
Raquel
R
Riveira-Muñoz
Eva
E
Escaramís
Georgia
G
Julià
Antonio
A
Marsal
Sara
S
Martín
José Ezequiel
JE
González-Gay
Miguel Angel
MA
Balsa
Alejandro
A
Raya
Enrique
E
Martín
Javier
J
Estivill
Xavier
X
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors
D055233:Cornified Envelope Proline-Rich Proteins; C524768:LCE3C protein, human