Thrombin-Activatable Fibrinolysis Inhibitor Polymorphisms and Cerebral Venous Thrombosis in Mexican Mestizo Patients.

Thrombin-activatable fibrinolysis inhibitor (TAFI) gene polymorphisms have been proposed as a predisposing factor for cerebral venous thrombosis (CVT). We analyzed the association between CVT and TAFI single-nucleotide polymorphisms (rs3742264, rs2146881, and rs1926447) compared to healthy controls. Mexico Mestizo confirmed cases with CVT and age- and sex-matched controls with no history of venous thrombotic events were recruited from July 2006 to July 2015. Demographic, clinical, and imaging information was included in the analysis. Genotyping single-nucleotide polymorphisms were performed by allele-specific polymerase chain reaction. Allelic univariate analysis, haplotype association, and Hardy-Weinberg equilibrium were assessed. A total of 113 CVT cases (94 females [83.2%]; median age 35 years [interquartile range 27-43 years]) and 134 age- and sex-matched controls were included. The main risk factors for CVT were pregnancy/puerperium (30.9%), oral contraceptive use (19.5%), and hereditary thrombophilia (7.1%). We found no significant association for heterozygous and homozygous models for rs3742264 ( P = .30 and P = .69, respectively), rs2146881 ( P = .90 and P = .17, respectively), or rs1926447 ( P = .40 and P = .52, respectively) compared to controls; these findings were consistent in subgroup and haplotype analyses. In conclusion, TAFI rs3742264, rs2146881, and rs1926447 polymorphisms do not increase the risk of CVT in comparison to healthy controls.

Mild hyperhomocysteinemia and low folate concentrations as risk factors for cervical arterial dissection.

BACKGROUND AND PURPOSE: Elevated homocysteine (Hcy) plasma levels are associated with an increased risk of spontaneous cervical artery dissection (sCAD). We examined the potential association between Hcy, folate, vitamin B(12) levels and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms in patients with cerebral infarct caused by sCAD. PATIENTS AND METHODS: 39 patients who survived a cerebral infarct caused by sCAD [20 (51%) women; 24 (61.5%) vertebral and 15 (38.5%) internal carotid arteries], and 76 healthy control subjects were included. Hcy plasma levels (fasting and after methionine load), folate and vitamin B(12) levels were measured. We also performed polymorphisms of MTHFR. Hcy, vitamin B(12), folates and polymorphisms of MTHFR were assessed and any associations were analyzed using multivariate statistics. RESULTS: Mean plasma fasting Hcy level was 9.81 mumol/l for cases and 6.38 for controls (p = 0.001). The occurrence of sCAD was associated with elevated fasting Hcy levels (>95th percentile over the control group) with an adjusted odds ratio of 7.9 (95% CI 1.66-35). The association between low plasma folate values (<5th percentile) and the presence of CAD was 7.9 (95% CI 1.6-31) after adjusting for confounding variables. The distribution of the MTHFR genotype showed a higher TT mutant frequency among CAD patients (p = 0.034). CONCLUSIONS: High plasma concentrations of Hcy and low plasma levels of folate were associated with an increased risk of sCAD in the sample studied. We conclude that deficiencies in nutritional status may contribute to the relatively high incidence of CAD in Mexico.

Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Elevated plasma levels of homocysteine are associated with an increased risk of deep-vein thrombosis. Through a case-control study, we examined the potential association among homocysteine, folate and vitamin B12 levels, and the common C677-->T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene in patients with cerebral venous thrombosis (CVT). METHODS: Forty-five patients with CVT and 90 control subjects were studied. Plasma levels of homocysteine (fasting and after methionine load), folate, and vitamin B12 were measured. Genotyping of the MTHFR gene was also performed. The estimated risk of CVT associated with hyperhomocysteinemia, low vitamin levels, and MTHFR mutation were expressed as odds ratio (OR) and its 95% CI (crude and after adjusting by other independent variables). RESULTS: The adjusted OR for CVT associated with high (>90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (<10th percentile) and presence of CVT was 3.5 (1.2 to 10.0) after adjustment for confounding factors. There was a higher frequency of MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant (P=0.098). Patients with MTHFR mutation and low folate levels presented the highest homocysteine levels. CONCLUSIONS: High plasma concentrations of homocysteine and low plasma folate levels were associated with an increased risk of CVT in this population in which low socioeconomic conditions and deficient nutritional status may contribute to its relatively high incidence.

Juvenile myoclonic epilepsy: linkage to chromosome 6p12 in Mexico families.

Juvenile myoclonic epilepsy is a common subtype of idiopathic epilepsy accounting for 4-11% of all epilepsies. We reported previously significant evidence of linkage between chromosome 6p12-11 microsatellites and the clinical epilepsy and EEG traits of JME families from Belize and Los Angeles. To narrow the JME region, we ascertained and genotyped 31 new JME families from Mexico using a later generation of Généthon microsatellites. Two point linkage analyses obtained significant Z(max) values of 3.70 for D6S1573 and 2.65 for D6S1714 at theta(m = f) = 0.10, and 3.49 for D6S465, 2.11 for D6S1960 at theta(m = f) = 0.05 assuming autosomal dominant inheritance with 70% age-dependent penetrance. Multipoint LOD score curve peaked at 4.21 for D6S1573. Haplotype and recombination analysis reduced the JME region to 3.5 cM flanked by D6S272 and D6S1573. These results provide confirmatory evidence that a major susceptibility gene for JME exists in chromosome 6p12 in Spanish-Amerinds of Mexico.