TM6SF2 RS58542926 IS LINKED TO THROMBOCYTOPENIA-RELATED ADVANCED HEPATIC FIBROSIS IN EGYPTIAN PATIENTS WITH CHRONIC HEPATITIS C

Thrombocytopenia in chronic hepatitis C (CHC) patients is a serious complication, which hinders starting and continuation of several invasive diagnoses and treatment protocols. This problem is multifactorial; therefore, it is important to explore host factors linked to it. Interestingly while we were investigating the association between rs58542926 polymorphism in TM6SF2 gene and both hepatic & extra hepatic changes, we found a significant association between TM6SF2 risk allele and thrombocytopenia in Egyptian CHC patients. There are 351 participants in this study. We measured gene expression of IL-6 and TNF-α in peripheral blood mononuclear cells (PBMCs) and plasma thrombopoietin (TPO) level in 20 CHC patients with advanced fibrosis. The minor allele was linked to elevated thrombocytopenia (TCP), and lower TPO levels. These findings raise concerns regarding the effect of this polymorphism on different diagnostic techniques and the outcomes of hepatitis C virus (HCV) treatment. In conclusion, we demonstrated for the first time that the occurrence of the minor allele of the rs58542926 polymorphism is associated not only with hepatic but also with extrahepatic (thrombocytopenia) alterations in CHC Egyptian patients, allowing for the use of this variant as a pharmacogenetic marker to recognize CHC patients who have a high possibility for developing late stages of liver fibrosis and extrahepatic complications.