title: Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study.
abstract: OBJECTIVE
  Potential causes of cryptogenic cerebrovascular (CV) events are patent foramen ovale (PFO) and hyper homocysteinemia (H-Hcys), this latter a well-established risk factor for thrombosis particularly in the presence of mutation for the methylenetetrahydrofolate reductase (MTHFR) gene. This study investigated if in uncomplicated hypertensive subjects (HTs) with isolated PFO and H-Hcys, a different MTHFR polymorphism pattern for C667→T gene mutation could influence PFO management and to reduce the CV risk.
  
  
  METHODS
  In thirty-two HTs aged 55.6±14.4years, PFO was diagnosed by echocardiography. MTHFR genotype was evaluated by a multiplex polymerase chain reaction with reverse line blot hybridization assay. In relation to the T allele distribution, HTs were divided in normal (CC), heterozygote (CT) and homozygote (TT) for the MTHFR genotype. All subjects received a supplementation of oral folate (5mg daily) and were evaluated yearly for 2years. Analysis of variance for repeated measures (ANOVA) was used to compare changes of Hcys at baseline and at the end of follow-up and differences between continuous variables were evaluated in the three MTHFR groups with the Tukey's post hoc test after adjustment for confounders.
  
  
  RESULTS
  At the follow-up, Hcys levels significantly normalized from baseline both in TT (38.1±6.7 vs. 15±3.6, p<0.01) and CT (26.6±2.3 vs. 9.2±1.6, p<0.01) but not in CC subjects (18.2±1.8 vs. 16.0±1.6, NS). Independently of age, BMI, vitamin treatment both systolic and diastolic blood pressure (BP) significantly decrease at the follow-up in all the MTHFR genotypes. No CV events were observed during the follow-up.
  
  
  CONCLUSIONS
  In HTs with isolated PFO and H-Hcys, oral folate supplementation reduces Hcys levels both in TT and CT subjects with C667→T mutation of MTHFR. In addition the BP normalization probably contributed to reduce CV risk in these genotypes.
authors.affiliation: Department of Internal Medicine, Santa Maria della Misericordia Hospital, Rovigo, Italy. mazza.alberto@azisanrovigo.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Mazza
authors.forename: Domenico
authors.initials: D
authors.lastname: Montemurro
authors.forename: Roberto
authors.initials: R
authors.lastname: L'Erario
authors.forename: Mauro
authors.initials: M
authors.lastname: Chinaglia
authors.forename: Cristian
authors.initials: C
authors.lastname: Piergentili
authors.forename: Silvio
authors.initials: S
authors.lastname: Aggio
authors.forename: Francesco
authors.initials: F
authors.lastname: Zanon
authors.forename: Gianni
authors.initials: G
authors.lastname: Pastore
authors.forename: Ada
authors.initials: A
authors.lastname: Zanier
authors.forename: Gaia
authors.initials: G
authors.lastname: Grassetto
authors.forename: Sergio
authors.initials: S
authors.lastname: Zamboni
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001794:Blood Pressure; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D016009:Chi-Square Distribution; D017548:Echocardiography, Transesophageal; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D054092:Foramen Ovale, Patent / Q000150:complications* / Q000000981:diagnostic imaging; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D007558:Italy; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D014815:Vitamins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)