Single nucleotide polymorphic alleles of human DP-2 gene for detection of susceptibility to hair growth inhibition by PGD2
DP-2 antagonists reversed PGD 2 -mediated human hair growth inhibition in a dose-dependent manner in vitro by reducing PGD 2 -triggered apoptosis and maintaining proliferation of keratinocytes. Hair follicles from approximately half of the alopecia patients exhibited little susceptibility to PGD 2 's effect in vitro. SNPs in the human DP-2 gene were identified that are associated with hair growth inhibition by PGD 2 . These findings underscore the role of DP-2 in regulating hair growth and indicate that DP-2 can be an effective approach in preventing and/or treating androgenetic alopecia in patients sensitive to PGD 2 . Furthermore, the SNPs identified here can be used to identify patients who will benefit from treatment.
1. A method of treatment of androgenetic alopecia, baldness or hair loss in a subject that is identified to be likely to be responsive to administration of a DP-2 antagonist that is a selective DP-2 antagonist with respect to DP-1 to stimulate hair growth, comprising:
(i) genotyping single nucleotide polymorphic loci within or flanking the DP-2 gene in a genomic DNA sample obtained from the subject, wherein single nucleotide polymorphic loci rs545659, rs634681, and rs7167 are genotyped;
(ii) determining whether the subject is likely to be responsive to administration of the DP-2 antagonist, based on the genotype detected at each of the loci rs545659, rs634681, and rs7167, wherein the subject is likely to be responsive to administration of the DP-2 antagonist if the subject carries minor alleles for each of the single nucleotide polymorphic loci rs545659, rs634681, and rs7167; and
(iii) administering the DP-2 antagonist to the subject who carries minor alleles for each of the single nucleotide polymorphic loci rs545659, rs634681, and rs7167.
2. The method of claim 1 , further comprising the step of obtaining the genomic DNA sample from the subject.
3. The method of claim 1 , wherein genotyping comprises the step of sequencing the genomic DNA regions that contain the loci.
4. The method of claim 1 , wherein genotyping comprises the steps of:
(i) contacting the genomic DNA with one or more detectably labeled oligonucleotides complementary to an allele at said loci; and
(ii) detecting the presence or absence of the allele at said loci.
5. The method of claim 2 , comprising the step of amplifying the genomic DNA by PCR.
6. The method of claim 5 , wherein genotyping comprises the step of sequencing the amplified genomic DNA regions that contain the loci.
7. The method of claim 5 , wherein genotyping comprises the steps of:
(i) contacting the amplified genomic DNA with one or more detectably labeled oligonucleotides complementary to an allele at said loci; and
(ii) detecting the presence or absence of the allele at said loci.
8. The method of claim 5 , wherein the subject has hair loss associated with androgenetic alopecia, discoid lupus erythematosis, congenital hypotrichosis, lichen planopilaris or scarring alopecia.
9. The method of claim 1 , wherein the DP-2 antagonist is setipiprant, AM211, ramatroban, an indole acetic acid derivative, a phenyl acetic acid derivative, or a tetrahyrdroquinoline derivative.