Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6.
A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OR(Overall) = 1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR = 1.27 (1.16-1.34)) and Mongolian (OR = 2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis.
Center for Genomic Regulation and Public Health and Epidemiology Network Biomedical Research Center, CIBERESP, Barcelona, Spain.
Eva
E
Riveira-Munoz
Su-Min
SM
He
Georgia
G
Escaramís
Philip E
PE
Stuart
Ulrike
U
Hüffmeier
Catherine
C
Lee
Brian
B
Kirby
Akira
A
Oka
Emiliano
E
Giardina
Wilson
W
Liao
Judith
J
Bergboer
Kati
K
Kainu
Rafael
R
de Cid
Batmunkh
B
Munkhbat
Patrick L J M
PL
Zeeuwen
John A L
JA
Armour
Annie
A
Poon
Tomotaka
T
Mabuchi
Akira
A
Ozawa
Agnieszka
A
Zawirska
A David
AD
Burden
Jonathan N
JN
Barker
Francesca
F
Capon
Heiko
H
Traupe
Liang-Dan
LD
Sun
Yong
Y
Cui
Xian-Yong
XY
Yin
Gang
G
Chen
Henry W
HW
Lim
Rajan P
RP
Nair
John J
JJ
Voorhees
Trilokraj
T
Tejasvi
Ramón
R
Pujol
Namid
N
Munkhtuvshin
Judith
J
Fischer
Juha
J
Kere
Joost
J
Schalkwijk
Anne
A
Bowcock
Pui-Yan
PY
Kwok
Giuseppe
G
Novelli
Hidetoshi
H
Inoko
Anthony W
AW
Ryan
Richard C
RC
Trembath
André
A
Reis
Xue-Jun
XJ
Zhang
James T
JT
Elder
Xavier
X
Estivill
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
D055233:Cornified Envelope Proline-Rich Proteins; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C549748:LCE3B protein, human; C524768:LCE3C protein, human