PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma

Abstract

Single-nucleotide polymorphisms (SNPs) of the programmed cell death protein-1 (PDCD1), programmed cell death protein-1 ligand-1 (PDCD1LG1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) genes are implicated in the pathogenesis of some cancers. We investigated the role of PDCD1, PDCD1LG1, and CTLA4 SNPs in MM pathogenesis and the susceptibility to and clinical features of multiple myeloma (MM). We obtained genomic DNA from 124 patients with MM and 211 healthy controls and detected PDCD1 (rs36084323, rs41386349, and rs2227982), PDCD1LG1 (rs2297136 and rs4143815), and CTLA4 (rs733618, rs11571316, rs231775, and rs3087243) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method or the TaqMan allelic discrimination real-time PCR method. The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323/rs41386349/rs2227982) compared with the healthy controls. PDCD1 rs2227982 CC genotype was associated significantly with a higher frequency of bone lesions. Patients with PDCD1LG1 rs2297136 TT and TC types (high-expression types) showed lower albumin level than those with CC genotype. In addition, the PDCD1LG1 rs4143815 CC and CG types (high-expression types) were associated significantly with higher frequency of patients who were treated with thalidomide and/or bortezomib. However, there was no statistical significance between CTLA4 polymorphisms and clinical variables of patients with MM. There were no significant differences between all the polymorphisms and OS. Our study indicates that the PDCD1 haplotype is associated with a susceptibility to MM. The PDCD1 rs2227982 and PDCD1LG1 rs2297136 affect the clinical features of multiple myeloma patients.

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“…PDCD1 encodes the Programmed cell death protein-1 (PD-1), which expresses in the activated T cells. The interaction between PD-1 and its ligand PD-L1 (encoded by PDCD1LG1) suppresses the activation of lymphocytes and cytokine production 61 . Inhibitors of PD-1 and PD-L1 have shown great clinical benefits in some types of cancer 62 .…”

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“…Certain single nucleotide polymorphisms (SNPs) in genes such as PDCD1 (coding for programmed cell death) Rs41386349, this SNP was previously considered as a hot point for Grave's disease and Addison's disease [15], rheumatoid arthritis (RA) [16], Kawasaki disease [17], multiple myeloma [18] and variant A for rs41386349 affects susceptibility of chronic HBV [19]. Whereas, only PD-L1 rs1411262C/T gene polymorphism in the case of Grave's disease and Addison's disease [15], increased rheumatoid factor seropositivity [16] and a higher probability of Kawasaki disease [17] was discovered.…”

“…Whereas, only PD-L1 rs1411262C/T gene polymorphism in the case of Grave's disease and Addison's disease [15], increased rheumatoid factor seropositivity [16] and a higher probability of Kawasaki disease [17] was discovered. The multiple myeloma occurs more often with a PDCD1 GCC/GCC haplotype (rs36084323/rs41386349/rs2227982) variant [18]. PDCD1 (rs7421861) has been studied in case of esophageal cancer [20] and chronic HBV infection, its oncogenicity [19] as well as RA [16].…”

“…GG genotype variant altered tumour necrosis factor-a (TNF-a) to increase levels in HBV patients [38]. PDCD-1.9 (rs2227982) has been evaluated in terms of breast cancer [39], ovarian cancer [40], ankylosing spondylitis [41], multiple myeloma [18] and chronic HBV infection and its oncogenity [19]. This polymorphism increases the probability and severity of the disease in case of ankylosing spondylitis and breast cancer [39,41].…”

“…Simultaneously, the same reserchers have found that C > T variant reduces the risk of breast cancer [39] and raises the risk of ovarian cancer [40]. CC genotype variant was significantly correlated with a higher frequency of osteolysis [18]. This gene polymorphism may have a significant influence on hepatocarcinogenesis [19].…”