Fibronectin gene polymorphisms in HCV related type II mixed cryoglobulinemia: risk of development of B-cell lymphoma

Abstract

B-cell non-Hodgkin lymphoma (B-NHL) are clonal malignancies with diverse clinical presentations, pathogenesis, and biologic behavior. Hepatitis C virus (HCV) is a major leading cause of liver-related morbidity and B-cell lymphoproliferative diseases such as mixed cryoglobulinemic syndrome (MCns) and B-NHL. Fibronectin (FN) is a multifunctional glycoprotein of 250 kDa which is encoded on a gene that is 75 kb in length, located on chromosome 2q34–36 and consists of 50 exons. Polymorphisms of the fibronectin gene are as follows: HindIII, HaeIII, TaqI, and MspI. The aim of the current study was to investigate the possible link between the two FN polymorphisms (called MspI "CC genotype, CD genotype and DD genotype" and HaeIII "AA genotype, AB genotype and BB genotype") and the development of lymphoma in HCV-positive patients with mixed cryoglobulinemic syndrome compared to healthy age- and sex-matched individuals. The present study included 75 patients; 25 HCV-positive patients with MCns and 50 B-NHL patients, in addition to 25 healthy controls. To achieve this aim, genotyping for FN gene was done by PCR-RFLP technique and screening for HCV infection was performed by ELISA and confirmed by RT-PCR, cryoglobulins have been detected by cold precipitation (4 °C for 72–96 h) and plasma FN levels have been assessed by ELISA. The study revealed that HaeIII-AB genotype can be considered as a risk factor for NHL development and high HaeIII-A allele frequency seems to be associated with NHL development. We did not find any significant difference between all patients' groups and controls regarding MspI genotyping. It was also found that plasma FN level did not show any significant difference between B-NHL patients and each of HCV positive patients with MCns and controls. Our study provides further evidence for the role of HaeIII-AB FN gene polymorphism as a risk factor for B-NHL development in sub-population of Egyptian HCV-positive patients with MCns. We also found that HaeIII-A allele has been significantly increased in overall B-NHL patients.

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