The Heterozygous GT Genotype of SNP rs3754217 in the Extracellular Matrix Protein 1 (ECM1) Gene Could Be a Protective Factor against HBV-Related Cirrhosis

Introduction: Hepatitis B virus (HBV) infection remains a major public health problem despite the introduction of a universal HBV vaccination several years ago. Thus, the high endemicity, observed especially in developing countries, particularly in Togo, underlines the urgent need for further research into the mechanisms explaining the diversity of clinical outcomes of HBV in this region. The analysis of genetic factors appears particularly relevant for identifying prognostic markers and for better understanding the progression of this infection to severe forms. This study characterized these extracellular matrix protein 1 (ECM1) gene polymorphisms rs3834087 and rs3754217 and their association with the progression of HBV in Togo. Methodology: Genotyping of the ECM1 gene polymorphisms rs3834087 and rs3754217 were performed on 141 participants, including 90 cases (25 with chronic hepatitis B, 41 with cirrhosis, and 24 with hepatocellular carcinoma) and 51 healthy controls, using real-time PCR with the QuantStudio^TM 5 Real-Time PCR system. Allelic discrimination was performed using TaqMan software Genotyper. Results: The frequencies of the GAG/GAG, GAG/-, and -/- genotypes of the ECM1 gene polymorphism rs3834087 were 5.67%, 7.80%, and 86.52%, respectively. Furthermore, the frequency of the wild-type GAG allele was 9.57%, while that of the mutated allele was 90.42%. The rs3754217 gene polymorphism exhibited GG, GT, and TT genotype frequencies of 31.91%, 58.86%, and 9.21%, respectively. Its wild-type G allele was 61.34%, while that of the mutated T allele was 38.65%. The results show that a potential protective effect against the progression of a severe infection was associated with the GT genotype of rs3754217 in the subgroup of chronic HBV towards severe forms, including hepatic cirrhosis, with an OR of 0.33 and a 95% CI of 0.10 - 1.03, p = 0.04. Conclusion: The present study is the first investigation conducted in Togo to evaluate the association between the ECM1 gene polymorphisms rs3834087 and rs3754217 and the progression of HBV infection. It showed that the GT heterozygous genotype of rs3754217 is associated with protection against the progression of chronic hepatitis B to cirrhosis.