Oxidative stress-related enzyme polymorphisms associated with the immunological biomarkers levels in heavy drinkers in Taiwan.

BACKGROUND: Excessive alcohol intake can result in the oxidative stress in cells and the genetic variations of alcohol-metabolizing enzymes are responsible for the different degrees of toxicity of alcohol in several organs, such as the liver and immunological systems. We hypothesized that the alteration of oxidative stress due to some genetic variations of oxidative stress-related enzymes could result in changes of specific biomarkers, and heavy drinkers could be cautioned about the predictive likelihood to induce drinking-induced diseases. METHODS: A total of 108 heavy drinkers and 106 nonheavy drinkers were enrolled and the hematological, biochemical, and immunological tests were measured; the genotypes of oxidative stress-related enzymes, including manganese superoxide dismutase (MnSOD1183T>C), glutathione peroxidase 1 (GPX1Pro198Leu), catalase (CAT-262C>T), and myeloperoxidase (MPO-463G>A), were assayed by real-time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: For the males, the levels of carbohydrate-deficient transferrin (CDT), malondialdehyde (MDA), CD4(+), immunoglobulin G (IgG), immunoglobulin M (IgM), and IL-6 were significantly different between the two groups. Furthermore, there were higher proportions of CD19(+) cells and lower TNF-α levels in heavy drinkers with the MnSOD C carriers, and there were higher percentages of CD19(+) cells and IL-6 levels in heavy drinkers with the combined genotypes of MnSOD C carriers and MPO A carriers. CONCLUSIONS: Our findings indicate that heavy drinkers may be cautioned predictive likelihood for them to induce drinking-induced diseases by analyzing their MnSOD genotypes and immunological biomarkers.

Effects of whey protein concentrate (WPC) on the distributions of lymphocyte subpopulations in rats with excessive alcohol intake.

To investigate the effects of whey protein concentrate (WPC) on antioxidant statuses and the lymphocyte subpopulations in the rats with alcohol intake, the antioxidant statuses in the peripheral blood (PB) and the lymphocyte subpopulations in the PB, spleen, and bone marrow (BM) of the rats fed with WPC (0.334 g/kg) and alcohol (6 g/kg) for 3 months were analyzed. Results showed that the effects of WPC on the glutathione peroxidase and glutathione in the PB, the T and B cells in the spleen, and the B cells in the BM were more apparent in the rats with alcohol intake; however, they are not apparent in the controls. Taken together, our results indicated that the immunity of rats might be enhanced by the increased antioxidant ability after WPC supplementation and the effects of WPC on the lymphocyte subpopulations were mainly in the spleen and BM and not in the PB.

Epistasis of oxidative stress-related enzyme genes on modulating the risks in oral cavity cancer.

BACKGROUND: The aim of this study was to evaluate the risks of the polymorphisms of oxidant stress-related enzymes on patients with oral cavity cancer by genotyping of manganese superoxide dismutase (MnSOD [1183T>C]), myeloperoxidase (MPO [-463G>A]), catalase (CAT [-15A>T]) and glutathione peroxidases 1 (GPx1 [Pro198Leu]). METHODS: A case-control study was conducted on 122 biopsy-proven oral cavity cancer patients with, at least, one of the past habits of cigarette smoking, alcohol drinking or betel-quid chewing, and 122 approximately age- and habit-matched controls. RESULTS: The independent risks of the polymorphisms for each enzyme on carcinogenicity were non-significant. The 2-order gene-gene interactions of the polymorphisms, assessed by using a logistic regression model, on risk did not show significant changes, neither. However, the epistasis, assessed by multifactor dimensionality reduction (MDR) for three-order (CAT, MnSOD, and MPO) and four-order was significant. Additionally, the fact that the levels of O(2)(-), GSSG and total GSH in the patients were significantly different according to certain genotypes which revealed that the polymorphisms of these enzymes could affect these parameters to some extent. CONCLUSIONS: The results suggested that the genetic-effects of the polymorphisms of these enzymes could slightly modify the risk in oral cavity cancer development individually, but significantly when they functioned together.

Roles of the genetic polymorphisms of alcohol-metabolizing enzymes on the immunology in high-risk drinkers.

Alcohol metabolism involves several enzymes and the individual genetic variations in the alcohol metabolism are related to the absorption, distribution, and elimination of alcohol and metabolites such as acetaldehyde. Therefore, the genetic variations of alcohol-metabolizing enzymes are responsible for the different toxicity of alcohol in several organs like liver and immunological systems. The purpose of this study was to evaluate if the life styles such as drinking and smoking and the genetic variations of alcohol-metabolizing enzymes (ADH2, ALDH2, CYP2E1, and CAT) were associated with the immunological biomarkers. In this study, 105 high-risk drinkers and 102 low-risk drinkers who were excluded from the immune-related diseases and other critical diseases were enrolled to evaluate the immunological functions. Counts of white blood cells, mononuclear cells, and lymphocyte subpopulations, and liver and immunological function tests were measured. Genotypes of alcohol-metabolizing enzymes were assayed by a real-time PCR and PCR-restriction fragment length polymorphism. Generally, the activity of aspartate aminotransferase (AST) was higher than that of alanine aminotransferase (ALT) in alcoholics; however, the activities of AST and ALT were simultaneously elevated in general hepatitis except for alcohol-induced hepatitis. Thus, the higher ratio of AST/ALT was used to be a marker for the alcohol-induced abnormal liver function. Glutamyltransferase (GGT) is produced by the liver cell microsomes and is a useful laboratory marker as an indicator of early liver cell damage. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. In addition, the synergistic effects of smoking and drinking on the count of white blood cell (WBC) and mononuclear cells were found to be significant. Furthermore, there were higher OR to become high-risk drinkers in subjects with the combination of ALDH2 (*1/*1) genotype and either genotype of ADH2 or CYP2E1 than the others with other combinations of genotypes. Additionally, there were more abnormal immunological tests in the subjects with higher activity of ADH2 and lower activity of ALDH2. Our results suggested that the habits of drinking, smoking, and betel chewing, and genetic variations of alcohol metabolism were associated with the immunological biomarkers.

Emergence of G9 serotype rotavirus as a major cause of infectious gastroenteritis in southern Taiwan.

Infectious gastroenteritis is a common illness in children. This study investigated the etiology and clinical manifestations of hospitalized children with symptoms of infectious gastroenteritis in southern Taiwan. We studied 467 consecutive patients with infectious gastroenteritis aged from 2 days to 10 years hospitalized from April 2001 to March 2002. Rotavirus was the most common etiology (57%) of infectious gastroenteritis in these patients. Bacterial infection was noted in 57 cases (12%). Rotavirus was found in 92% of nosocomial infectious gastroenteritis (p < or = 0.001). Bloody stool was a presentation of bacterial infection in 74% of cases and rotavirus gastroenteritis in 8% of cases (p < or = 0.001). The G serotype of rotavirus was identified in 87 patients. Serotype G1 was the most common (51%), followed by G9 (31%). The emergence of serotype G9 strains in rotavirus infection has not been previously reported from Taiwan. Incorporation of G9 rotavirus into vaccines should be considered.