5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension

Maura Ravera, Francesca Viazzi, Valeria Berruti, Giovanna Leoncini, Paola Zagami, Gian Paolo Bezante, Nadia Rosatto, Roberto Ravazzolo, Roberto Pontremoli, Giacomo Deferrari

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI ≥125g/m 2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P <.02) and carotid plaque (TT, 42% v CT + CC, 21%; P <.05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (TT, 0.79 ± 0.05 mm ν CT + CC, 0.67 ± 0.02 mm; P <.02), relative wall thickness (TT, 0.23 ± 0.01 mm ν CT + CC, 0.20 ± 0.005 mm; P <.02), and surface area (TT, 19 ± 1.9 mm 2 ν CT + CC, 15 ± 0.55 mm 2; P <.05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r 2 = 0.11, F = 9.7, dF = 1-205, P <.0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalAmerican Journal of Hypertension
Volume14
Issue number4 I
DOIs
Publication statusPublished - 2001

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Methylenetetrahydrofolate Reductase (NADPH2)
Alleles
Hypertension
Genotype
Albumins
Retinal Vessels
Blood Pressure
Creatinine
Urine
Ophthalmoscopy
Albuminuria
Cytosine
Left Ventricular Hypertrophy
Carotid Arteries
Point Mutation
Gene Frequency
Thymidine
Genes
Habits
Blood Vessels

Keywords

  • 5,10-Methylenetetrahydrofolate reductase polymorphism
  • Organ damage
  • Primary hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Ravera, M., Viazzi, F., Berruti, V., Leoncini, G., Zagami, P., Bezante, G. P., ... Deferrari, G. (2001). 5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension. American Journal of Hypertension, 14(4 I), 371-376. https://doi.org/10.1016/S0895-7061(00)01296-6

5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension. / Ravera, Maura; Viazzi, Francesca; Berruti, Valeria; Leoncini, Giovanna; Zagami, Paola; Bezante, Gian Paolo; Rosatto, Nadia; Ravazzolo, Roberto; Pontremoli, Roberto; Deferrari, Giacomo.

In: American Journal of Hypertension, Vol. 14, No. 4 I, 2001, p. 371-376.

Research output: Contribution to journalArticle

Ravera, M, Viazzi, F, Berruti, V, Leoncini, G, Zagami, P, Bezante, GP, Rosatto, N, Ravazzolo, R, Pontremoli, R & Deferrari, G 2001, '5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension', American Journal of Hypertension, vol. 14, no. 4 I, pp. 371-376. https://doi.org/10.1016/S0895-7061(00)01296-6
Ravera, Maura ; Viazzi, Francesca ; Berruti, Valeria ; Leoncini, Giovanna ; Zagami, Paola ; Bezante, Gian Paolo ; Rosatto, Nadia ; Ravazzolo, Roberto ; Pontremoli, Roberto ; Deferrari, Giacomo. / 5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension. In: American Journal of Hypertension. 2001 ; Vol. 14, No. 4 I. pp. 371-376.
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T1 - 5,10-methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension

AU - Ravera, Maura

AU - Viazzi, Francesca

AU - Berruti, Valeria

AU - Leoncini, Giovanna

AU - Zagami, Paola

AU - Bezante, Gian Paolo

AU - Rosatto, Nadia

AU - Ravazzolo, Roberto

AU - Pontremoli, Roberto

AU - Deferrari, Giacomo

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N2 - Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI ≥125g/m 2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P <.02) and carotid plaque (TT, 42% v CT + CC, 21%; P <.05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (TT, 0.79 ± 0.05 mm ν CT + CC, 0.67 ± 0.02 mm; P <.02), relative wall thickness (TT, 0.23 ± 0.01 mm ν CT + CC, 0.20 ± 0.005 mm; P <.02), and surface area (TT, 19 ± 1.9 mm 2 ν CT + CC, 15 ± 0.55 mm 2; P <.05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r 2 = 0.11, F = 9.7, dF = 1-205, P <.0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

AB - Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI ≥125g/m 2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P <.02) and carotid plaque (TT, 42% v CT + CC, 21%; P <.05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (TT, 0.79 ± 0.05 mm ν CT + CC, 0.67 ± 0.02 mm; P <.02), relative wall thickness (TT, 0.23 ± 0.01 mm ν CT + CC, 0.20 ± 0.005 mm; P <.02), and surface area (TT, 19 ± 1.9 mm 2 ν CT + CC, 15 ± 0.55 mm 2; P <.05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r 2 = 0.11, F = 9.7, dF = 1-205, P <.0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

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