IL17A and IL23R gene polymorphisms affect the clinical features and prognosis of patients with multiple myeloma

Abstract

Single nucleotide polymorphisms (SNPs) in interleukin 17 (IL17A) and IL-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. We investigated the influence of IL17A and IL23R SNPs on the risk of developing multiple myeloma (MM) and its clinical features. We obtained genomic DNA from 120 patients with MM and 201 healthy controls and detected IL17A -197 G/A (rs2275913) and IL23R H3Q (rs1884444) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant differences in the genotype and allele frequencies of IL17A -197 G/A and IL23R H3Q between the controls and patients with MM. Compared with the GG and GA genotypes, the IL17A AA genotype was significantly associated with lower hemoglobin levels. The IL23R HH genotype was significantly associated with higher frequency of bone lesions and plasmacytoma than the HQ and QQ genotypes. We observed significant differences in overall survival (OS) between patients treated with thalidomide and/or bortezomib and those treated conventionally. Therefore, we also examined the effect of IL17A and IL23R polymorphisms on the clinical variables and OS in patients treated with thalidomide and/or bortezomib. We observed that the IL23R HH genotype was significantly associated with poor survival compared with the QH and HH genotypes in these patients. Our findings indicate that IL17A -197 G/A and IL23R H3Q are not associated with susceptibility to MM. However, IL-17 and IL-23R polymorphisms may affect severity, bone lesions, and extra-medullary disease in patients with MM. Moreover, IL23R polymorphisms may contribute to poor prognosis in patients with MM treated with thalidomide and/or bortezomib.

Association between interleukin gene polymorphisms and multiple myeloma susceptibility

“…The published dates of all research studies varied from 2000 to 2018. Most of the research was conducted within Caucasian communities: 10 studies in Caucasian populations (62.5%) (20,22,23,25,(33)(34)(35)(36)(37)(38), 3 within Asian populations (18.75%) (17,39,40) and 3 in Mixed Afro-American populations (18.75%) (24,41,42). Of note, the quantitative TaqMan method (TaqMan PCR) was often used to detect the SNP state with control references (11 studies, 68.75%) (20,(22)(23)(24)(25)(36)(37)(38)(39)41,42).…”

“…Of note, the quantitative TaqMan method (TaqMan PCR) was often used to detect the SNP state with control references (11 studies, 68.75%) (20,(22)(23)(24)(25)(36)(37)(38)(39)41,42). Also, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 5 studies (31.25%) (17,(33)(34)(35)40). The variables from sixteen relevant case-control studies were contained 2,597 cases and 3,851 controls.…”

“…The variables from sixteen relevant case-control studies were contained 2,597 cases and 3,851 controls. Source controls were mainly selected by population-based method with age/sex-matched (12 studies, 75%) (17,20,(23)(24)(25)33,34,36,38,(40)(41)(42). Regarding the NOS methodological quality, all included studies were of high quality with ≥7 out of 10 (mean 8.02 point).…”

“…In Total, 16 published studies had detected interleukin polymorphism of IL-1β, IL-1α, IL-4, IL-6, IL-6R, IL-10, IL-10R, IL-17 and IL-23 in the prediction of MM patients. In more details, 2 studies had identified the relationship between the SNP of IL-1α/β (22,36), one study of IL-4 37, ten studies of IL-6 and IL-6R (20,(22)(23)(24)(25)34,(37)(38)(39)42), four studies of IL-10 and IL-10R (17,23,33,37), three studies of (IL-17 39-41) and one IL-23R polymorphisms 17. The majority of SNP associations were reported by Birmann et al (20).…”

“…Recently, a multivariable analysis was used to determine if interleukin family polymorphisms are a prognostic factor for survival in MM patients (17)(18)(19). It has been widely reported that many different polymorphisms in different loci are related to poor survival and prognosis of MM (19,20).…”