Alanine Amino Transferase Concentrations Are Linked to Folate Intakes and Methylenetetrahydrofolate Reductase Polymorphism in Obese Adolescent Girls

Frelut, Marie-Laure; Emery-Fillon, Nathalie; Guilland, Jean-Claude; Dao, Hunh Han; Courcy, G. Potier De

doi:10.1097/01.mpg.0000228110.83616.92

Cited by 18 publications

(20 citation statements)

References 49 publications

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“…We did not observe any significant change in aminotransferases activities in neither tissue tested, despite the relevant oxidative and histological alterations found in our study. Conversely, Frelut et al (2006) recently showed a positive correlation between ALT activity and Hcy plasma levels in obese adolescent girls. Experimental models of hyperhomocysteinemia in rats provide evidence for increased serum ALT and AST activities, associated with ROS production and hepatic lipid peroxidation (Huang et al, 2001; Woo et al, 2006).…”

Section: Discussionmentioning

confidence: 95%

“…Liver injury could be identified by serum markers, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are increased as a result of hepatic necrosis (Ozer et al, 2008). Hcy has been related to hepatotoxic conditions in numerous reports, which have showed a positive correlation between hyperhomocysteinemia and plasma aminotransferases activities in clinical and experimental studies (Huang et al, 2001; Woo et al, 2006; Frelut et al, 2006). In this context, an increase of ALT and AST activities was observed in serum of hyperhomocisteinemic rats (Woo et al, 2006) and of ALT in plasma hyperhomocysteinemic patients (Frelut et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Matté

Stefanello

Mackedanz

et al. 2009

Intl J of Devlp Neuroscience

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Hyperhomocysteinemia has been related to various diseases, including homocystinuria, neurodegenerative and hepatic diseases. In the present study we initially investigated the effect of chronic homocysteine administration on some parameters of oxidative stress, named total radical-trapping antioxidant potential, total antioxidant reactivity, catalase activity, chemiluminescence, thiobarbituric acid-reactive substances, and total thiol content in liver of rats. We also performed histological analysis, evaluating steatosis, inflammatory infiltration, fibrosis, and glycogen/glycoprotein content in liver tissue sections from hyperhomocysteinemic rats. Finally, we evaluated the activities of aminotransferases in liver and plasma of hyperhomocysteinemic rats. Wistar rats received daily subcutaneous injection of Hcy from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, liver and plasma were collected. Hyperhomocysteinemia decreased antioxidant defenses and total thiol content, and increased lipid peroxidation in liver of rats, characterizing a reliable oxidative stress. Histological analysis indicated the presence of inflammatory infiltrate, fibrosis and reduced content of glycogen/glycoprotein in liver tissue sections from hyperhomocysteinemic rats. Aminotransferases activities were not altered by homocysteine. Our data showed a consistent profile of liver injury elicited by homocysteine, which could contribute to explain, at least in part, the mechanisms involved in human liver diseases associated to hyperhomocysteinemia.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Matté

Stefanello

Mackedanz

et al. 2009

Intl J of Devlp Neuroscience

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“…Previous researches could also elicit positive association of obesity and hypertension, coronary artery disease or liver diseases with MTH-FR C677T mutations [32][33][34]. Also Thwnashom et al have reported that folic acid and MTHFR gene polymorphism were found to be significantly related to the overweight/obese and control groups in logistic regression analysis [35].…”

Section: Discussionmentioning

confidence: 99%

Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region

et al. 2009

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Abstract.Background: This work was planned to check for the association of polymorphisms related to methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with overweight/obesity among Saudi subjects from Qassim region. Methods: This work included 130 subjects having overweight or obesity and 111 normal controls. Their age mean ± SD was 27 ± 9.8 and 24 ± 8.8 years respectively. Their DNA was analyzed for polymorphisms of MTHFR; 677C/T and 1298 A/C and ACE; I/D genes using real-time PCR. Results: Genotype and allele frequencies of studied polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to that of controls. However, on analysis of body mass index (BMI), cases showed slightly higher but statistically nonsignificant mean ± SD values among those carrying the mutant MTHFR 677 T allele (CT + TT vs. CC, 30.7 ± 4.5 vs. 29.9 ± 4.9), 1298 C allele (AC + CC vs. AA, 29.9 ± 4.1 vs. 29.7 ± 5.5) and ACE D allele (ID + DD vs. II, 30.0 ± 5.1 vs. 29.1 ± 2.8). In addition controls having the DD and ID genotypes showed higher statistically significant values of BMI than those of the II genotype (22.0 ± 1.9, 21.7 ± 2.6 and 19.5 ± 2.3 respectively, p < 0.05). Conclusion: There is no solid association of polymorphisms related to MTHFR and ACE genes with non-complicated overweight or obesity among Saudi subjects from Qassim Region.

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“…Furthermore, in anti-hepatitis C virus antibody seropositive individuals, Wang et al found that smoking and higher alcohol consumption independently elevated serum ALT level (38). Moreover, liver damage in obese adolescent girls was enhanced by low folate status and the MTHFR C677T mutation (39).…”

Section: Discussionmentioning

confidence: 99%

Folate Deficiency Was Associated with Increased Alanine Aminotransferase and Glutamyl Transpeptidase Concentrations in a Chinese Hypertensive Population: A Cross-Sectional Study

Wei

Cao

et al. 2016

J Nutr Sci Vitaminol

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Summary Alanine aminotransferase (ALT), aspartate transaminase (AST), and glutamyl transpeptidase (GGT) were three key enzymes in the hepatic metabolism. This study aimed to investigate the effect of homocysteine (Hcy) metabolism gene polymorphisms and serum Hcy and folate level on the hepatic functions in a Chinese hypertensive population. A representative sample with 480 subjects aged 28-75 was enrolled in 2005.9-2005.12 from six hospitals in different Chinese regions. Serum ALT, AST and GGT were measured by using an automatic biochemistry analyzer. Serum Hcy was measured by high-performance liquid chromatography, and serum folate was measured by chemiluminescent immunoassay. Known genotypes were detected by PCR-RFLP methods. The results showed that the MTHFR C677T mutation was related a decreased serum AST level (r520.11, p50.026), whereas the MTHFR A1298C mutation elevated serum AST level (r50.11, p50.032). Furthermore, multiple regression analysis showed that folate deficiency was associated with higher serum ALT (b (SE): 0.13 (0.06), p50.031) and GGT level (b (SE): 0.18 (0.07), p50.011). However, serum Hcy level may not affect the hepatic functions. Our data suggested that hepatic functions were affected by MTHFR gene polymorphisms and serum folate level. Further studies are needed to confirm these correlations in a larger population. Key Words folate deficiency, MTHFR gene polymorphisms, alanine aminotransferase, aspartate transaminase, glutamyl transpeptidase Fatty liver disease (FLD), including primary non-alcoholic fatty liver disease (NAFLD) and the severe form, non-alcoholic steatohepatitis (NASH) is the most common form of liver disease and is increasing throughout the world (1). In Western adults, the prevalence of NAFLD assessed by ultrasound is 20-30% and the prevalence of NASH is 3-16% (2). Alanine aminotransferase (ALT), aspartate transaminase (AST) and glutamyl transpeptidase (GGT) are three key enzymes in the liver metabolism. Studies showed that high levels of ALT, AST and GGT were associated with liver disease (3). Furthermore, serum ALT and AST levels showed relevance with the histopathological changes in liver biopsies of hepatitis C patients (4). In one carbon metabolism, folate is closely related to many important biochemical processes in vivo. A mouse experiment suggested that maternal low folate and selenium diet altered liver gene expression patterns in the offspring after weaning (5). And a previous study showed that folate supplementation reduced the serum ALT level in high baseline ALT (.40 IU/L) individuals (6). In addition, a higher serum homocysteine (Hcy) level also showed strongly correlation with liver disease (7,8).Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) are three key regulatory enzymes in the folate and Hcy metabolisms (9). MTHFR catalyses the reduction of 5,10-methylenetetrahydrofolate (5,10-MTHF) to 5-methyltetrahydrofolate (5-MTHF) and 5-MTHF is a cofactor for Hcy methylation to methionine when cata...

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Alanine Amino Transferase Concentrations Are Linked to Folate Intakes and Methylenetetrahydrofolate Reductase Polymorphism in Obese Adolescent Girls

Abstract: Our data suggest that folate intake and the MTHFR polymorphism represent a part of the link between antioxidant status and liver disease in obese adolescent girls.

Cited by 18 publications

References 49 publications

Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region

Folate Deficiency Was Associated with Increased Alanine Aminotransferase and Glutamyl Transpeptidase Concentrations in a Chinese Hypertensive Population: A Cross-Sectional Study

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