Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study.
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.
Mazza
Alberto
A
Department of Internal Medicine, Santa Maria della Misericordia Hospital, Rovigo, Italy. mazza.alberto@azisanrovigo.it
Montemurro
Domenico
D
L'Erario
Roberto
R
Chinaglia
Mauro
M
Piergentili
Cristian
C
Aggio
Silvio
S
Zanon
Francesco
F
Pastore
Gianni
G
Zanier
Ada
A
Grassetto
Gaia
G
Zamboni
Sergio
S
Rubello
Domenico
D
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
D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)