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

English (OpenAlex)

Leptin (LEP), a hormone, is primarily produced by white adipose cells in the body.By affecting energy expenditure and food intake, it has a significant effect on maintaining body weight homeostasis (6).In addition, LEP has various other functions in the body, such as influencing insulin resistance, cell proliferation, oxidative stress, cancer cell inflammation, apoptosis, and immune regulation (7).LEP is found in human peripheral blood, cord blood, and BM blood.Various studies have shown that high levels of LEP may affect the onset and progression of many malignancies.LEP exerts its biological effect by binding to and activating leptin receptors (LEPR).The LEP gene is on chromosome 7q31.3.The leptin receptor 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 LEP gene 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 LEP was 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.