Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study

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• 作者：Alberto Mazza ; Domenico Montemurro ; Roberto L'Erario ; Mauro Chinaglia ; Cristian Piergentili ; Silvio Aggio ; Francesco Zanon ; Gianni Pastore ; Ada Zanier ; Gaia Grassetto ; Sergio Zamboni ; Domenico Rubello
• 关键词：Genetics ; Hypertension ; Homocysteine ; Patent foramen ovale
• 刊名：Microvascular Research
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：80
• 期：3
• 页码：545-548
• 全文大小：212 K

文摘

Objectives

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 ± 14.4 years, 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 (5 mg daily) and were evaluated yearly for 2 years. 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.