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S Redler,
F Albert,
F F Brockschmidt,
C Herold,
S Hanneken,
S Eigelshoven,
K A Giehl,
R Kruse,
G Lutz,
H Wolff,
B Blaumeiser,
M Böhm,
T Becker,
M M Nöthen,
R C Betz
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ABSTRACT: 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 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, since many of these association findings were derived from small patient samples. Objective: To investigate association between AA and selected cytokine genes using a sample of 768 AA patients 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 IL-1B, IL-1A, IL-1RN, 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 IL-10, IL-36RN, IL-12B, IL-6, IL-2, IL-23, IL-2RA, and IL-4R. Results: Significant association was found for two variants within both IL-2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL-2RA variant rs706778 (P = 0.00038), and the TNF/LTA locus variant rs1800629 (P = 0.0017). In subgroup analyses, according to severity, age of 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 IL-2RA 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.
British Journal of Dermatology 08/2012; · 3.67 Impact Factor
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ABSTRACT: steatocystoma multiplex (SM) is a rare disorder of the pilosebaceous unit characterized by the eruption of numerous sebum-containing dermal cysts. Most cases are sporadic, however, also familial cases with autosomal dominant inheritance have been described.(1) The etiopathogenesis of SM remains elusive but there are several hypotheses to explain its cause such as origin from sebaceous retention cysts, or representing a nevoid malformation of the pilosebaceous duct.
British Journal of Dermatology 05/2012; · 3.67 Impact Factor
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S Redler,
F F Brockschmidt,
R Tazi-Ahnini,
D Drichel,
M P Birch,
K Dobson,
K A Giehl,
S Herms,
M Refke,
N Kluck,
R Kruse,
G Lutz,
H Wolff,
M Böhm,
T Becker,
M M Nöthen,
A G Messenger,
R C Betz
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ABSTRACT: The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified.
To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors.
Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus.
Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups.
The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.
British Journal of Dermatology 02/2012; 166(6):1314-8. · 3.67 Impact Factor
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S Redler,
M P Birch,
D Drichel,
K Dobson,
F F Brockschmidt,
R Tazi-Ahnini,
K A Giehl,
N Kluck,
R Kruse,
G Lutz,
H Wolff,
T Becker,
M M Nöthen,
A G Messenger,
R C Betz
British Journal of Dermatology 06/2011; 165(3):703-5. · 3.67 Impact Factor
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S Redler,
F F Brockschmidt,
L Forstbauer,
K A Giehl,
C Herold,
S Eigelshoven,
S Hanneken,
J De Weert,
G Lutz,
H Wolff,
R Kruse,
B Blaumeiser,
M Böhm,
T Becker,
M M Nöthen,
R C Betz
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ABSTRACT: 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).
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.
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.
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.
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.
British Journal of Dermatology 04/2010; 162(4):866-9. · 3.67 Impact Factor
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S. Redler,
F.F. Brockschmidt,
L. Forstbauer,
K.A. Giehl,
C. Herold,
S. Eigelshoven,
S. Hanneken,
J. De Weert,
G. Lutz,
H. Wolff,
R. Kruse,
B. Blaumeiser,
M. Böhm,
T. Becker,
M.M. Nöthen,
R.C. Betz
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ABSTRACT: 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).Objectives To examine the role of the TRAF1/C5 locus in the development of AA using a large sample of 1195 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, Pcorr = 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.
British Journal of Dermatology 12/2009; 162(4):866 - 869. · 3.67 Impact Factor
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ABSTRACT: Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of isolated alopecia. The disorder is characterized by the absence or scarcity of scalp hair, eyebrows and eyelashes at birth. Coarse wiry hair begins to grow during childhood, but this is followed by progressive hair loss, which usually begins around puberty. A recent study identified mutations in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless gene. We investigated three reportedly unrelated Turkish multigeneration families with MUHH. Using direct sequencing of U2HR we were able to identify the c. 2T>A (p.M1K) mutation in one index patient of each family. The mutation cosegregates perfectly with the disease in all members of the families. To our knowledge, this is the first time that a mutation in U2HR has been identified in families from the Middle East. The observation of a common mutation is suggestive of a possible founder effect.
Clinical and Experimental Dermatology 12/2009; 34(8):e953-6. · 1.20 Impact Factor
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R C Betz,
K König,
A Flaquer, S Redler,
S Eigelshoven,
A-K Kortüm,
S Hanneken,
A Hillmer,
T Tüting,
J Lambert,
J De Weert,
R Kruse,
G Lutz,
B Blaumeiser,
M M Nöthen
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ABSTRACT: The functional R620W (c.1858C>T) variant of the protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) has been associated with a variety of autoimmune disorders. A recent study has suggested that R620W also contributes to the severe form of alopecia areata (AA).
We sought to replicate the finding of an association between PTPN22 and severe AA. In addition, we wanted to study the effect of PTPN22 on the general risk to develop AA and on other subtypes of AA (mild AA, early/late age at onset, positive/negative family history).
The R620W variant was genotyped in a large case-control sample of Belgian-German origin with 435 patients and 628 controls.
Significant results were obtained for the overall collective of patients with AA (P=0.007). Subdividing the sample according to severity of AA, family history and age at onset, we detected lowest P-values for patients with the severe form of AA (Pcorr=0.036), with a positive family history (Pcorr=0.042) and with an age at onset<or=20 years (Pcorr=0.048).
Our results suggest the R620W variant of PTPN22 as a general risk factor in AA with the strongest effect observed among patients with a severe type of AA, a positive family history or an early onset of disease.
British Journal of Dermatology 02/2008; 158(2):389-91. · 3.67 Impact Factor
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R.C. Betz,
K. König,
A. Flaquer, S. Redler,
S. Eigelshoven,
A.‐K. Kortüm,
S. Hanneken,
A. Hillmer,
T. Tüting,
J. Lambert,
J. De Weert,
R. Kruse,
G. Lutz,
B. Blaumeiser,
M.M. Nöthen
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[hide abstract]
ABSTRACT: Background The functional R620W (c.1858C>T) variant of the protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) has been associated with a variety of autoimmune disorders. A recent study has suggested that R620W also contributes to the severe form of alopecia areata (AA).Objectives We sought to replicate the finding of an association between PTPN22 and severe AA. In addition, we wanted to study the effect of PTPN22 on the general risk to develop AA and on other subtypes of AA (mild AA, early/late age at onset, positive/negative family history).Methods The R620W variant was genotyped in a large case–control sample of Belgian–German origin with 435 patients and 628 controls.Results Significant results were obtained for the overall collective of patients with AA (P = 0·007). Subdividing the sample according to severity of AA, family history and age at onset, we detected lowest P-values for patients with the severe form of AA (Pcorr = 0·036), with a positive family history (Pcorr = 0·042) and with an age at onset ≤ 20 years (Pcorr = 0·048).Conclusions Our results suggest the R620W variant of PTPN22 as a general risk factor in AA with the strongest effect observed among patients with a severe type of AA, a positive family history or an early onset of disease.
British Journal of Dermatology 11/2007; 158(2):389 - 391. · 3.67 Impact Factor
