Role of MIF-173G/C and Mbl2 Codon 54A/B Variants in the Risk of Multiple Myeloma: An Association Study

Abstract

Background: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. Objective: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. Methods: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. Results: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF-173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). Conclusion: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.

Impact of Exon 1 Polymorphism in the MBL2 Gene on MBL Serum Levels and Infection Susceptibility in Acute Lymphoid Leukemia

“…While no correlation was found between serum MBL levels and MBL2 gene polymorphisms in this study, the observed serum MBL levels in the study group (mostly < 500 ng/mL) were considerably lower than the typical levels found in the general population (> 2000 ng/mL) (Baioumy et al, 2021;Izakovicova et al, 2023;Pehlivan et al, 2021). This suggests a serum MBL de ciency among ALL patients, regardless of their genotype.…”

“…For example, a study of patients with myeloid leukemia in Turkey found that the A/A genotype was more frequent (0.64) than the O/O genotype (0.17) (Sokołowska et al, 2020). Another study of patients with multiple myeloma conducted in Polish found that the A/A genotype (0.73) and B/B genotype (0.88) were more frequent than the O/O genotype (0.19) (Pehlivan et al, 2021). In this study, we observed a signi cantly lower frequency of the B/B genotype (0.08) than the frequencies reported in the aforementioned studies.…”