Association of methylenetetrahydrofolate reductase C677T and cystathionine ß-synthase polymorphisms in cardiovascular disease in the algerian population.

AIM: Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and cystathionine ß-synthase (CBS) genes, involved in the intracellular metabolism of homcysteine, can result in hyperhomocysteinemia. The objective of this study was to evaluate prevalence estimates of MTHFR C677T and the CBS insertion of 68-bp (844ins68) polymorphisms among individuals with cardiovascular disease (CVD). METHODS: In total, 131 patients (61 men and 70 women) were hospitalized in the Cardiology Department in CHU of Sétif, Algeria. The control group included 147 apparently healthy adults (82 women and 65 men). The genetic analysis of the MTHFR C677T polymorphism was performed by real-time polymerase chain reaction on a Light Cycler; the CBS genotype was analyzed by polymerase chain reaction in a thermal cycler. RESULTS: The frequency of the TT genotype was 16.1% in the patient group and 14.3% in the control group. The CT genotype constituted 43.5% and 40.1% in the patient group and the control group, respectively. There was no significant difference in the occurrence of the TT genotype between the studied groups. The frequency of C677T/MTHFR in male and female patients was 16.4% and 15.7% for the TT genotype, respectively. There was no significant difference in T allele frequencies between sexes. However, the frequency of C677T homozygotes in the patients was higher in men with CVD than that in corresponding control subjects (40.2% vs. 29.2%), but the difference was not statistically significant. The coexistence of the MTHFR 677TT genotype and the common CBS 844ins68 variant was lower among patients. CONCLUSIONS: The MTHFR C677T and CBS 844ins68 variants tested in this study, individually or combined, are not associated with CVD in the Algerian population.

The prevalence of methylenetetrahydrofolate reductase 677 C-T, factor V 1691 G-A, and prothrombin 20210 G-A mutations in healthy populations in Setif, Algeria.

The polymorphic mutation 677 C-T in the methylenetetrahydrofolate reductase (MTHFR) gene presents a heterogeneous worldwide distribution and is associated with different disorders such as cardiovascular disease. Its frequency shows great ethnic and geographic variations. The aim of this work is to determine the frequency of MTHFR 677 C-T and coexistence of MTHFR 677 C-T with 2 other common, hereditary thrombophilia causes-namely, factor V 1691 G-A and prothrombin (PT) 20210 G-A mutation-in the Sétif region of Algeria. The study involved 147 apparently healthy participants (82 men and 65 women). Genotyping was carried out by a real-time polymerase chain reaction. The MTHFR 677T carrier frequency was found to be 54.4% (80/147); 59 individuals were heterozygous (40.1%), and 21 were homozygous (14.3%). The frequency of MTHFR 677T was found to be 34.3%. Among the 147 individuals, 3 (2.0%) had factor V Leiden, and 5 (3.4%) had PT 20210 A mutation. Of the 80 participants with MTHFR 677T mutation, 2 had heterozygote factor V 1691 G-A gene mutation, and 4 had heterozygote PT 20210 G-A gene mutation. The results showed that MTHFR 677T prevalence is quite high: an allelic frequency of 34.3% with a genotype frequency of 14.3%. Factor V 1691 G-A and PT 20210 G-A gene mutations are rare in the healthy population of the Sétif region of Algeria.

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and cystathionine beta-synthase genes as a risk factor for neural tube defects in Sétif, Algeria.

BACKGROUND: Neural tube defects (NTD) are severe congenital malformations due to a failure in neural tube formation at the beginning of pregnancy. The etiology of NTD is multifactorial, with environmental and genetic determinants. We suggest a study of gene-gene interactions regarding the possible association of NTD with specific mutations of 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes. PATIENTS AND METHODS: The genetic analysis of the MTHFR C677T polymorphism was performed by real-time polymerase chain reaction (PCR) on a Light Cycler, the CBS genotype was analyzed by PCR in a thermal cycler. Ninety-two mothers who had conceived NTD children and 48 fathers were investigated. A group of 147 adults, including 82 apparently healthy women, was used as control. RESULTS: Among control mothers, 35 (43%) were heterozygous for the C677T variant and 14 (17%) were TT homozygous. Among the cases, 25 (52%) out of 48 mothers and 22 (46%) out of 48 fathers carried the T allele; 9 mothers (19%) and 5 fathers (10%) had the TT genotype. A homozygous C677T mutation was not an NTD risk factor in this preliminary study in an Algerian population; a possible gene-gene interaction between the MTHFR C677T polymorphism and the CBS 844ins68 has also been examined in relation to NTD, but no such association has been shown. There was a statistically significant difference between the heterozygosity genotype frequency of CBS polymorphisms in mothers with a previous child with NTD compared with the mother controls (odds ratio: 3.72; 95% CI: 1.59-8.73). CONCLUSION: Our results with Algerian NTD mothers did not show a significant association for any group, suggesting that the thermolabile variant C677T in the MTHFR gene is not a risk factor for a mother to have NTD offspring; rather, folic acid supplementation or fortification should become mandatory for all women of reproductive age in Algeria.

Prognostic value of homocysteinemia in patients with congestive heart failure.

BACKGROUND: Elevated plasma homocysteine levels are associated with increased risk of vascular disease and of congestive heart failure (CHF), with a relationship between homocysteine values and disease severity. Hyperhomocysteinemia is a risk factor for cardiac dysfunction. In this study, the predictive value of elevated homocysteine levels was investigated in the prognosis of ischemic and non-ischemic CHF. METHODS: A total of 159 patients with CHF, 89 with non-ischemic and 70 with ischemic CHF (83% males, mean age 62 years, mean ejection fraction 27%), and 119 controls (79% males, mean age 59.8 years) had fasting blood samples taken to measure plasma homocysteine, vitamin B(12) and folate levels. Coronary angiography was performed for all patients. The mean duration of follow-up was 49.6+/-36.7 months. RESULTS: As in other studies, the mean level of homocysteinemia was significantly higher in the CHF group (15.80 micromol/L) than in the control group (10.90 micromol/L) (p=0.001) whatever the etiology (non-ischemic, 16.11+/-6.84 micromol/L; ischemic, 15.41+/-6.45 micromol/L). This result was observed without vitamin deficiency, but in patients, the mean creatinine value was moderately higher than in controls. We found a positive correlation between plasma homocysteine levels and New York Heart Association (NYHA) classification, creatinine and age. Moreover, hyperhomocysteinemia appears to be a powerful predictive factor of mortality in CHF patients (relative risk of death, 4.23; p=0.0003). In the follow-up of this study, 41.5% of patients with homocysteinemia >17 micromol/L died vs. 21.3% of patients with levels <17 micromol/L. In multivariate analysis, when homocysteine levels were adjusted for a second parameter (age, NYHA, creatinine, diabetes), the risk of death remained significant after each adjustment. CONCLUSIONS: Elevated homocysteine levels observed in CHF patients, whatever the etiology of their heart disease (ischemic or non-ischemic), were correlated with the severity of the disease. Hyperhomocysteinemia appears to be a predictive factor of mortality in CHF patients.