How Effective are leptin Gene Polymorphisms and Methylation during the Course of Multiple Myeloma?

Abstract

Leptin is mainly produced from adipose tissue and released into the circulation. Circulating leptin binds to the leptin receptor (LEPR) in the brain, which activates signaling pathways that inhibit feeding and promote calorie expenditure. The leptin receptor (LEPR, also known as Ob-R) gene is located at chromosome 1p31. DNA methylation consists of addition a methyl group at position 5′ of the pyrimidine ring of the cytosines upstream of a guanine (dinucleotide CpG) catalyzed by DNA methyltransferases. Methylation of cytosine in CpG sites is an important epigenetic modification way that could suppress the gene expression. This study was conducted to reveal the role of leptin (-2548 G/A, rs7799039) and LEPR (-668 A/G, rs113711) gene polymorphisms in patients diagnosed with multiple myeloma (MM). Patients who were diagnosed with MM and followed-up in our clinic between January 2010 and January 2022 were included in the study. The genotypes of the leptin (-2548 G/A, rs7799039) and LEPR (-668 A/G, rs113711) genes were statistically compared between patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined. In addition, the methylation status of the patients was compared to the healthy control group, and the effect on survival was evaluated. A total of 300 patients diagnosed with MM and 170 individuals to form a healthy control group were included in this study. In the statistical analysis performed to investigate the effect of leptin and LEPR gene polymorphisms on disease susceptibility, GA and AA genotypes of the leptin gene were found to be significantly higher in the patient group compared to healthy controls. In the statistical analysis for -31 NT and -51 NT methylation of the leptin gene, -51 NT methylation was found to be significantly higher in healthy controls (p = 0.002). In the survival analysis, progression-free survival (PFS) of patients with GG genotype of the LEPR gene was found to be significantly shorter compared to others, there was no effect on the overall survival. In the multivariate analysis, it was revealed that the PFS of patients with GG genotype of the LEPR gene was 2.02 times shorter compared to others (RR: 2.017; CI: 1.191–3.418, p = 0.009). MM and leptin polymorphisms have significant features in terms of both disease susceptibility and treatment response.