Relationship of LEP, LEPR Variants, and LEP Methylation with Multiple Myeloma and Prognosis

Abstract

Introduction: Leptin (LEP) and LEP receptor (LEPR) play roles in cancer progression. We evaluated LEP-2548G/A and LEPR 668 A/G variants in patients with multiple myeloma (MM). In addition, the methylation status of CpG sites at 31 and 51 nucleotides (nt) according to the transcription start region of the LEPgene was examined. Methods: DNA was extracted from the peripheral blood of study participants who were healthy controls and patients with MM. These variants were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The methylation at -31 and -51 nt in the LEPwas performed using the methylation-specific PCR method. The 2-year progression-free survival (PFS) and 2-year overall survival (OS) were evaluated according to prognostic factors. Results: There was no significant difference in the genotype distributions of LEPR 668A/G and LEP-2548G/A between the control and patient groups (p>0.05). We found that -31 and -51 nt regions of the LEP gene were unmethylated in the patient group compared with the control group (p=0.051 and p=0.001, respectively). The -31 nt methylation was unchanged in 15 patients (78.94%). PFS and OS were higher in these patients than in the others. In multivariate analysis, the methylated/unmethylated ratio at -31 nt methylation was associated with a poor prognosis (p=0.020). Conclusion: To our knowledge, our study is the first to examine these variants and their methylation status in Turkish patients with MM. Our results showed that LEP gene -31 nt unmethylation was associated with PFS and OS. These results need to be confirmed in different ethnic and larger sample groups.

Keywords

• multiple myeloma
• leptin
• leptin receptor
• pcr-rflp
• ms-pcr