Fine mapping of the human AR/EDA2R locus in androgenetic alopecia

Abstract

MMP, which shows IgG and IgA antibodies to the carboxylterminus of BP180. 4 A further 10-20% of cases of MMP are antilaminin 332 MMP, which shows IgG antibodies to laminin 332 (previously called epiligrin or laminin 5). 5,6 Ocular MMP shows exclusive ocular mucosal lesions, although the autoantigen for this group has not been clearly identified.Although ocular lesions are commonly seen in MMP, they are usually hyperaemia or erosions which result in symblepharon or epithelialization over the cornea. A clear blister on the bulbar conjunctiva is rarely seen. In our case, a clear solitary blister appeared on the bulbar conjunctiva of the left eye without apparent hyperaemia or erosion. This blister quickly disappeared without any scar formation after the treatment of prednisolone and dapsone was initiated. In addition, a unique clinical feature of our case was the excellent effectiveness of dapsone on all the mucosal and skin lesions.Another interesting result for this case was the unique reactivity in immunoblot analysis using purified laminin 332. We have shown that the IgG antibodies in patients with antilaminin 332 MMP react with the three subunits of laminin 332, i.e. the a3 subunit, b3 subunit and c2 subunit, in various patterns. 2 In particular, most patient sera react with both the 165-kDa and 145-kDa forms of the processed a3 subunit, but not with the 200-kDa unprocessed a3 subunit. In our preparation of laminin 332, the 200-kDa unprocessed a3 subunit is not present. The 145-kDa protein is considered to be a degradation product from the 165-kDa processed a3 subunit, although it is not known where the digested 20-kDa fragment resides in the 165-kDa processed a3 subunit. In the previous study, 2 most patient sera reacted with both the 165-kDa and 145-kDa proteins, indicating that the epitopes for these sera are present on the domain common for both proteins. In contrast, the serum of the present case reacted only with the 165-kDa protein, but not with the 145-kDa protein, indicating that the epitope for this serum is present on the 20-kDa fragment which is digested by some protease. Therefore, it is worthwhile identifying the position of the 20-kDa fragment within the 165-kDa form of the processed a3 subunit. From the results of our previous reports, 1,7 the 20-kDa fragment is assumed to correspond to the domain IIIa region of the 165-kDa form of the processed a3 subunit. A study using recombinant proteins of the a3 subunit is now going on to confirm this speculation.

A Tale of Two Haplotypes: The EDA2R/AR Intergenic Region is the Most Divergent Genomic Segment between Africans and East Asians in the Human Genome

“…A number of polymorphisms across the 540KB region and in the nearby androgen receptor (AR) gene have been associated with androgen alopecia (AGA), also called male pattern baldness [Hillmer et al 2005;Hillmer et al 2008a;Hillmer et al 2008b;Hillmer et al 2009;Brockschmidt et al 2010]. The variant with the most significant AGA association (~10 -25 ), rs12558842, is one of the 52 haplotype-defining SNPs [Brockschmidt et al 2010].…”

“…The variant with the most significant AGA association (~10 -25 ), rs12558842, is one of the 52 haplotype-defining SNPs [Brockschmidt et al 2010]. When…”

“…Brockschmidt et al [Brockschmidt et al 2010] corrected for this association in their study of Pre-print version. Visit http://digitalcommons.wayne.edu/humbiol/ after 1 February 2013 to acquire final version.…”

Molecular Genetics of Alopecias

“…Although the exact pathogenesis for AGA is not entirely clear, there is a strong genetic component for this condition, and so far, a total of 12 susceptibility loci have been revealed [55][56][57][58]. As implied by the name of this condition, several loci have indeed been found to be associated with androgen-dependent pathways [56,59]. Recently, a new study has reported, for the first time, on AGA risk loci, which include genes that are connected to the WNT signaling pathway [58].…”

Genetik der androgenetischen Alopezie

“…Die Autoren postulierten, dass der Assoziationsbefund im AR-Gen durch Kopplungsungleichgewicht mit Arg57Lys zu erklären sei. Diesen Befund konnte die in Deutschland durchgeführte, bislang umfangreichste Assoziationsanalyse (Betroffene n=673, Nichtbetroffene n=248) nicht bestätigen[8]. Die stärkste Assoziation wurde mit der zwischen AR und EDA2R gelegenen Variante rs12558842 gefunden (.…”