Investigation of selected cytokine genes suggests that IL2RA and the TNF/LTA locus are risk factors for severe alopecia areata.
BACKGROUND
Alopecia areata (AA) is the second most common cause of hair loss in humans, and has a genetically complex inheritance. The hypothesis that AA is autoimmune in nature is supported by previous studies. These report an association with specific HLA alleles, as well as genetic variants of other genes implicated in autoimmunity, such as various cytokine genes. However, these cannot yet be considered proven susceptibility loci, as many of these association findings were derived from small patient samples.


OBJECTIVE
To investigate the association between AA and selected cytokine genes using a sample of 768 patients with AA and 658 controls of Central European origin.


METHODS
Eleven single-nucleotide polymorphisms (SNPs) from cytokine genes implicated in previous AA studies were genotyped. These genes were IL1B, IL1A, IL1RN, MIF, IFNG and the TNF/LTA gene region. We also genotyped 15 SNPs selected from cytokine genes that have shown significant association with other autoimmune diseases. These genes were IL10, IL36RN, IL12B, IL6, IL2, IL23, IL2RA and IL4R.


RESULTS
Significant association was found for two variants within both IL2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL2RA variant rs706778 (P = 0·00038) and the TNF/LTA locus variant rs1800629 (P = 0·0017). In subgroup analyses, according to severity, age at onset and family history these effects were stronger in the severely affected patients, with the lowest P-values being obtained for rs706778 (P = 3·8 × 10(-6) ).


CONCLUSIONS
Our results point to the involvement of IL2RA and the TNF/LTA region in the aetiology of AA, in particular severe AA, and provide further support for the hypothesis that AA is autoimmune in nature.
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany.
S
S
Redler
F
F
Albert
F F
FF
Brockschmidt
C
C
Herold
S
S
Hanneken
S
S
Eigelshoven
K A
KA
Giehl
R
R
Kruse
G
G
Lutz
H
H
Wolff
B
B
Blaumeiser
M
M
Böhm
T
T
Becker
M M
MM
Nöthen
R C
RC
Betz
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; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People; D055815:Young Adult
D053645:Interleukin-2 Receptor alpha Subunit; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha