No association between MTHFR gene C677T/A1298C polymorphisms, serum folate, vitamin B12, homocysteine levels, and prostate cancer in an Algerian population.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate and homocysteine metabolism, which are necessary for DNA methylation and nucleotide synthesis. Genetic polymorphisms that reduce MTHFR activity have been linked to several diseases, including prostate cancer. In this study, we aimed to investigate whether MTHFR polymorphisms, along with serum levels of folate, vitamin B12, and homocysteine, are associated with prostate cancer risk in the Algerian population. METHODS: A total of 106 Algerian men with newly diagnosed prostate cancer and 125 healthy controls were included in this case-control study. The MTHFR C677T and A1298C polymorphisms were analyzed using PCR/RFLP and Real-Time PCR TaqMan® assays, respectively. Serum levels of folate, total homocysteine, and vitamin B12 were measured using an automatic biochemistry analyzer. RESULTS: We found no significant differences in the genotype frequency of A1298C and C677T between prostate cancer patients and controls. Moreover, serum levels of folate, total homocysteine, and vitamin B12 were not significantly associated with prostate cancer risk (p > 0.05). However, age and family history were identified as significant risk factors (OR = 1.178, p = 0.00 and OR = 10.03, p = 0.007, respectively). CONCLUSION: Our study suggests that MTHFR C677T and A1298C, as well as serum levels of folate, total homocysteine, and vitamin B12, are not associated with prostate cancer risk in the Algerian population. However, age and family history are significant risk factors. Further studies with a larger sample size are required to confirm these findings.

The methylenetetrahydrofolate reductase C677T and A1298C genetic polymorphisms and plasma homocysteine in Alzheimer's disease in an Algerian population.

BACKGROUND: The etiology of Alzheimer's disease (AD) is multifactorial. The most important challenge of research is the identification of potential biomarkers associated with AD pathogenesis that may significantly contribute to early diagnosis of the disease. We aim to explore an eventual association of the C677T and A1298C genetic polymorphisms in the MTHFR gene with AD risk in an Algerian population. METHODS: This case-control study involved comparing a group of 106 patients that had developed AD to another group of 104 non-demented individuals. The MTHFR genotypes were determined using PCR-RFLP method. Additionally, the homocysteine level was evaluated. RESULTS: Genotypes analysis did not show an association for both MTHFR677CT and 677TT variants with AD risk (OR = 1.12; p = 0.66; OR = 1.76; p = 0.09) respectively. As expected, the 677CC wild type genotype showed a protective role against AD (OR = 0.52; p = 0.03). For 1298AC MTHFR variant, the distribution of different genotypes did not show a statistical significant difference between the two cohorts. However the silmutaneous carrier, CT/AC presented association with AD (OR = 5.96; p = 0.05). On the other hand, carrier-state of MTHFR T allele showed a relationship with AD (OR = 1.98; p = 0.02). Additionally, hyperhomocysteinemia seems to be a risk factor for AD (OR = 1.08; p = 0.02). CONCLUSION: Our exploration reveals that the silmutaneous carrier, CT/AC, carrier-state of MTHFR T allele, and hyperhomocysteinemia seem to be risk factors for AD.

Arylamine N-acetyltransferase 2 gene polymorphism in an Algerian population.

BACKGROUND: The arylamine N-acetyltransferase 2 (NAT2) is a key enzyme in the biotransformation of xenobiotics. NAT2 gene polymorphisms have been associated with the risk of isoniazid hepatotoxicity and these polymorphisms change among different populations. AIM: The objective of this study is to investigate NAT2 polymorphisms in order to predict the prevalence of NAT2 phenotype in an Algerian population. SUBJECTS AND METHODS: Genotyping of NAT2 was done using a PCR-RFLP method. Haplotype was analysed using the software package PHASE, version 2.0. RESULTS: The major haplotypes were NAT2*5B (23.72%), NAT2*6 A (18.61%), NAT2*4 (14.60%) and NAT2*5 F (10%). The average of the expected slow acetylator phenotype was 53%. CONCLUSION: Our results suggest that the high frequency of slow acetylator phenotype requires investigation into its possible association with ATDH.

Hyperhomocysteinemia is a risk factor for Alzheimer's disease in an Algerian population.

BACKGROUND AND AIMS: There is growing evidence that increased blood concentration of total homocysteine (tHcy) may be a risk factor for Alzheimer's disease (AD). The present study was conducted to evaluate the association of serum tHcy and other biochemical risk factors with AD. METHODS: This is a case-control study including 41 individuals diagnosed with AD and 46 nondemented controls. Serum levels of all studied biochemical parameters were performed. RESULTS: Univariate logistic regression showed a significant increase of tHcy (p = 0.008), urea (p = 0.036) and a significant decrease of vitamin B12 (p = 0.012) in AD group vs. controls. Using multivariate logistic regression, tHcy (p = 0.007, OR = 1.376) appeared as an independent risk factor predictor of AD. There was a significant positive correlation between tHcy and creatinine (p <0.0001). A negative correlation was found between tHcy and vitamin B12 (p <0.0001). CONCLUSIONS: Our findings support that hyperhomocysteinemia is a risk factor for AD in an Algerian population and is also associated with vitamin B12 deficiency.

Polymorphisms in NAT2 gene and atherosclerosis in an Algerian population.

BACKGROUND AND AIMS: The etiology of atherosclerosis is multifactorial. Genetic and environmental factors are involved in the development of atherosclerosis. Human arylamine N-acetyltransferase 2 (NAT2) is an important metabolizing enzyme that exhibits genetic polymorphisms and modifies individual response and/or toxicity to many xenobiotics. We undertook this study to investigate the NAT2 polymorphisms in patients with atherosclerosis. METHODS: Genotyping for NAT2 alleles was performed using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) in 285 Algerian patients with atherosclerosis and 286 controls. RESULTS: There was no association between NAT2 polymorphisms and atherosclerosis risk. However, the haplotype NAT2(*)5F decreased susceptibility to the disease (p = 0.005, OR = 0.55, 95% CI = 0.37-0.84). The frequency of the slow acetylator phenotype was approximately 50% in both cases and controls. CONCLUSIONS: These results suggest that NAT2 polymorphisms may not be involved in the pathogenesis of atherosclerosis.

N-acetyltransferase 2 (Nat2) polymorphism in the sand rat Psammomys obesus.

Human arylamine N-acetyltransferase 1 (NAT1) and its homologue in rodents (Nat2) are polymorphic xenobiotic metabolizing enzymes and also seem to play a role in endogenous metabolism. NAT1 and Nat2 polymorphism was associated to cancers under xenobiotic procarcinogens metabolism as well as under endogenous substrate metabolism. This study investigated the p-aminobenzoic acid (PABA) -Nat2 catalytic activity and its polymorphism in liver homogenates of adult sand rats Psammomys obesus Cretzschmar, 1828. These Saharian sand rats develop high incidence of spontaneous cancers under standard laboratory diet. The average value of PABA-Nat2 specific activity tested in nine sand rats was significant (2.96 ± 2.16 nmoles/min/mg). The N-acetylation exhibited a bimodal distribution. There was a significant difference (p<0.01) between PABA-Nat2 activity in the fast acetylators group (4.10 ± 1.67 nmol/min/mg) and slow acetylators group (0.7 ± 0.27 nmol/min/mg). The percentage of the fast acetylator group was 66.66%. These results support the presence of Nat2 polymorphism in the liver of the strain sand rats Psammomys obesus. This strain is useful for investigating the role of Nat2 polymorphisms in susceptibility to cancers related to arylamine carcinogen exposures as well as to endogenous substrate metabolism.