The TRAF1/C5 locus confers risk for familial and severe alopecia areata.
BACKGROUND
Alopecia areata (AA) is a common hair loss disorder with a complex mode of inheritance. Autoimmune mechanisms are presumed to be crucial aetiologically. It is plausible that a number of autoimmune disorders may share a common genetic background. This phenomenon has been demonstrated in previous studies, which have shown an overlap of susceptibility alleles between AA and other autoimmune disorders. Recent studies have shown that genetic variants on the TRAF1/C5 (tumor necrosis factor receptor-associated factor 1, complement component 5) locus confer susceptibility to rheumatoid arthritis (RA).


OBJECTIVE
To examine the role of the TRAF1/C5 locus in the development of AA using a large sample of 1,195 patients with AA and 1280 controls.


METHODS
We genotyped the two most significant single nucleotide polymorphisms (SNPs) (rs10818488, rs2416808) from a former RA candidate gene study. After having obtained evidence for association, we performed a fine-mapping study and genotyped the locus with an additional 27 SNPs.


RESULTS
While no significant result was obtained for the overall sample, rs2416808 showed significant associations in the analysis of the subgroups with severe AA and with a positive family history. The most significant P-value for rs2416808 was in familial cases (P = 0.004, P(corr) = 0.026). The fine mapping revealed significant associations for four additional SNPs in the analysis of subgroups, with rs2416808 remaining the most significant marker.


CONCLUSIONS
Our results point to the involvement of the TRAF1/C5 locus in the aetiology of familial and severe AA, and provide further support for a shared aetiology between AA and other autoimmune disorders.
Redler
S
S
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127, Bonn, Germany.
Brockschmidt
F F
FF
Forstbauer
L
L
Giehl
K A
KA
Herold
C
C
Eigelshoven
S
S
Hanneken
S
S
De Weert
J
J
Lutz
G
G
Wolff
H
H
Kruse
R
R
Blaumeiser
B
B
Böhm
M
M
Becker
T
T
Nöthen
M M
MM
Betz
R C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000506:Alopecia Areata / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003182:Complement C5 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*; D055815:Young Adult
D003182:Complement C5; D005819:Genetic Markers; D047990:TNF Receptor-Associated Factor 1