Abstract
Human Gasdermin A (GSDMA), a member of gasdermin gene family, is mainly expressed in skin and stomach. Mutations in its mouse counterpart Gsdma3, were found to cause skin diseases characterized by hair loss/ alopecia. As human and mice genes share 75% sequence similarity, present study was designed to check whether natural variability in human GSDMA gene was associated with alopecia. Blood samples of 100 alopecia patients and 100 age matched controls were collected and genomic DNA Isolated. All the samples were genotyped for two GSDMA SNPs, rs7212938 (V128L) and rs200722398 (V253I) for distribution of alleles along with haplotype analysis. Out of the T and G allele of rs7212938, the G allele count was found to be significantly increased (0.29 to 0.39) among alopecia patients and out of G/A alleles at rs200722398, allele A count was found to be significantly increased (0.06 to 0.13) among alopecia patients. Further haplotype analysis revealed that haplotype combination TGTAGG of rs7212938 and rs200722398 enhanced the susceptibility to alopecia significantly among Punjabi men. Studies on large population sample, other interacting genes and mechanism underlying the observed enhanced susceptibility are required to delineate the role of the observed association between GSDMA alleles and relative risk of alopecia.
Highlights
Gasdermin superfamily is a gene group consisting of gasdermin family genes (GSDMA, GSDMB, GSDMC, GSDMD) and gasdermin related genes (DFNA5/GSDME and DFNB59)
The present study found an increase in G allele amongst alopecia patients
Alopecia is an inflammatory disease and in mice its association with pyroptosis gave the hint of association between alopecia and pyroptosis in humans
Summary
Gasdermin superfamily is a gene group consisting of gasdermin family genes (GSDMA, GSDMB, GSDMC, GSDMD) and gasdermin related genes (DFNA5/GSDME and DFNB59). All Gasdermins except DFNB59 show similarity in protein structure which consists of two domains, gasdermin N-terminal (NT) and gasdermin Cterminal (CT) that are connected by an unstructured loop. The positions of these terminals are well conserved among the gsdm (mice) and GSDM (human) gene family. GSDMA was the first GSDM family member to be identified in Rim mutant mice as a gene positioned near to Rim mutation that was causing abnormal skin and hair development in the animals [2]. The NT of GSDMA protein causes pore formation when it is cleaved by inflammatory caspase, into N (1 to 251 amino acids) and C (252 to 445 amino acids) terminals [4,5]. NT oligomerizes by binding to the cardiolipin proteins and creates pores in plasma membrane leading to pyroptotic cell death [6,7]
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