Association of GZMB polymorphisms and susceptibility to non-segmental vitiligo in a Korean population

Abstract

Non-segmental vitiligo (NSV) is the most common type of vitiligo, which is characterized by chronic and progressive loss of melanocytes. Genetic factors have been shown to play a key role in NSV in association and family studies. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells that play an important role in inducing apoptotic changes of target cells. Several recent studies have provided evidence that polymorphism in the GZMB gene might be associated with autoimmune disease. A total of 249 NSV patients and 455 healthy controls were recruited to determine whether single nucleotide polymorphisms (SNPs) [rs2236337 (3′ untranslated region, UTR), rs2236338 (Tyr247His), rs11539752 (Pro94Ala), rs10909625 (Lys80Lys), rs8192917 (Arg55Gln), and rs7144366 (5′ near gene)] in GZMB gene contribute to the risk of developing NSV. Genotyping was performed using a single 192.24 Dynamic Array IFC. Data were analyzed using EP1 SNP Genotyping Analysis software to obtain genotype calls. Among the six SNPs tested, five SNPs (rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917) showed significant association with NSV susceptibility. Among them, rs2236338, rs11539752, rs10909625, and rs8192917 remained a statistically significant association following multiple correction test. The five SNPs were located within a block of linkage disequilibrium. Haplotypes T–A–G–T–T and C–G–C–C–C consisting of rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917 demonstrated significant association with NSV. Our results suggest that GZMB polymorphisms are associated with the development of NSV.

Skin Interstitial Fluid and Plasma Multiplex Cytokine Analysis Reveals IFN-γ Signatures and Granzyme B as Useful Biomarker for Activity, Severity and Prognosis Assessment in Vitiligo

“…GzmB, a serine protease secreted by CTLs and natural killer cells, exhibits a pathological role in many autoimmune skin disorders, particularly in skin blisters diseases ( 39 , 40 ). GzmB polymorphism has been reported in the previous literature in non-segmental vitiligo ( 41 , 42 ) ( 43 ). Furthermore, aside from pro-apoptotic function, studies have shown that GzmB is responsible for the cleavage of the extracellular matrix that contributes to the collapse of hair follicle immune privilege in alopecia areata, a close disease to vitiligo ( 44 ).…”

Whole Genome Sequencing Provides New Insights Into the Genetic Diversity and Coat Color of Asiatic Wild Ass and Its Hybrids

“…GZMB encodes a member of the granzyme subfamily of proteins and part of the peptidase S1 family of serine proteases ( Turner et al, 2019 ), and GZMB was identified by the four methods simultaneously. GZMB is associated with human autoimmune diseases ( Xu et al, 2018 ; Jeong et al, 2021 ) and essential effector molecules for natural killer (NK)-cell cytotoxicity ( Kim et al, 2011 ). The resistance of cattle to nematode infection and innate immunity requires the participation of GZMB ( Van Meulder et al, 2013 ).…”

Effective natural inhibitors targeting granzyme B in rheumatoid arthritis by computational study

“…It is involved in the induction of apoptosis in target cells. ( 15 , 16 ) And It has been associated with a high incidence of autoimmune diseases, rectal cancer, breast cancer and other cancers ( 21 – 24 ). It has been shown that inhibition of MAPK signal transduction by GZMB silencing can reduce the expression of inflammatory factors, apoptosis-related factors (Bcl-2 and caspase) and angiogenesis-related factors (VEGF and bFGF), thus reducing the synovial tissue hyperplasia and articular cartilage tissue damage associated with RA ( 16 ).…”