PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma

• Published in: Clinical and experimental medicine Vol. 20; no. 1; pp. 51 - 62
• Main Authors: Kasamatsu, Tetsuhiro, Awata, Maaya, Ishihara, Rei, Murakami, Yuki, Gotoh, Nanami, Matsumoto, Morio, Sawamura, Morio, Yokohama, Akihiko, Handa, Hiroshi, Tsukamoto, Norifumi, Saitoh, Takayuki, Murakami, Hirokazu
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-02-2020; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; B7-H1 Antigen - genetics; Bone lesions; Bortezomib; Case-Control Studies; Cell death; CTLA-4 Antigen - genetics; CTLA-4 protein; Cytotoxicity; Female; Gene Expression Regulation, Neoplastic; Gene polymorphism; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Hematology; Humans; Internal Medicine; Lymphocytes T; Male; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - genetics; Oncology; Original Article; Pathogenesis; Polymerase chain reaction; Polymorphism, Single Nucleotide; Programmed Cell Death 1 Receptor - genetics; Restriction fragment length polymorphism; Single-nucleotide polymorphism; Survival Analysis; Thalidomide; Up-Regulation; Programmed cell death protein-1 ligand-1; Programmed cell death protein-1; Multiple myeloma; Polymorphism
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-019-00585-4

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.