Abstract
Background/AimHyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil.MethodOne hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week.ResultsAmong subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03).ConclusionOur results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.
Highlights
Homocysteine (Hcy) belongs to a group of molecules known as cellular thiols
Association was found between the methylenetetrahydrofolate reductase (MTHFR) genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05)
The presence of genotype TT of MTHFR C677T polymorphism was more common in Chronic Hepatitis C (CHC) genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of hepatitis C virus (HCV) genotype
Summary
Homocysteine (Hcy) belongs to a group of molecules known as cellular thiols. It is considered a “bad thiol” because its association with a variety of health conditions including cardiovascular disease, [1] end-stage renal disease, [2] neural tube defects, [3] and cognitive dysfunctions including Alzheimer disease [4]. One of the most common mutations, or polymorphisms, that are associated with a mild increase in plasma homocysteine (hyperhomocysteinemia) is the 677C®T substitution (an alanine to valine change) in the enzyme methylenetetrahydrofolate reductase (MTHFR). As a consequence of the MTHFR dysfunctions, an increased Hcy level in plasma has been expected which, in turn, produces a cytotoxic effect [8]
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