OBJECTIVE: To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking. DESIGN: Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated. PATIENTS AND METHODS: CA/CT dinucleotide repeat polymorphism, G(8002)A polymorphism and -3A/-4A polymorphism (-138 insertion/deletion) were examined in the gene coding for ET-1 (6p21.3) in 398 subjects: 192 normotensives (healthy volunteers) and 206 patients with essential hypertension. Normotension was verified by 24 h ambulatory blood pressure monitoring. RESULTS: Significant inner associations were observed between all three polymorphisms, which suggests possible complex interactions inside the gene. The only significant difference in a single gene case control study was in the lengths of allelic variants of CA/CT dinucleotide repeat polymorphism. In hypertensive patients, the alleles of G(8002)A and -3A/-4A ET-1 polymorphisms were found to be significantly associated (G with -3A and A with -4A). None of the ET-1 gene polymorphisms was associated with BMI. A highly significant increase of the -3A allele of the -3A/-4A ET-1 polymorphism was found in hypertensive men who were current smokers or had smoked at least seven cigarettes a week for at least one year at any time in their life compared with hypertensive men who had never smoked (odds ratio 1.54, 95% CI 1.03 to 2.32, P=0.009). CONCLUSIONS: Smoking seems to be an independent cardiovascular risk factor genetically codetermined by the ET-1 gene variant.
OBJECTIVE: To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking. DESIGN: Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated. PATIENTS AND METHODS: CA/CT dinucleotide repeat polymorphism, G(8002)A polymorphism and -3A/-4A polymorphism (-138 insertion/deletion) were examined in the gene coding for ET-1 (6p21.3) in 398 subjects: 192 normotensives (healthy volunteers) and 206 patients with essential hypertension. Normotension was verified by 24 h ambulatory blood pressure monitoring. RESULTS: Significant inner associations were observed between all three polymorphisms, which suggests possible complex interactions inside the gene. The only significant difference in a single gene case control study was in the lengths of allelic variants of CA/CT dinucleotide repeat polymorphism. In hypertensivepatients, the alleles of G(8002)A and -3A/-4A ET-1 polymorphisms were found to be significantly associated (G with -3A and A with -4A). None of the ET-1 gene polymorphisms was associated with BMI. A highly significant increase of the -3A allele of the -3A/-4A ET-1 polymorphism was found in hypertensivemen who were current smokers or had smoked at least seven cigarettes a week for at least one year at any time in their life compared with hypertensivemen who had never smoked (odds ratio 1.54, 95% CI 1.03 to 2.32, P=0.009). CONCLUSIONS: Smoking seems to be an independent cardiovascular risk factor genetically codetermined by the ET-1 gene variant.
Entities:
Keywords:
Body mass index; Endothelin-1; Essential hypertension; Gene polymorphism; Smoking
Authors: R S Ames; H M Sarau; J K Chambers; R N Willette; N V Aiyar; A M Romanic; C S Louden; J J Foley; C F Sauermelch; R W Coatney; Z Ao; J Disa; S D Holmes; J M Stadel; J D Martin; W S Liu; G I Glover; S Wilson; D E McNulty; C E Ellis; N A Elshourbagy; U Shabon; J J Trill; D W Hay; E H Ohlstein; D J Bergsma; S A Douglas Journal: Nature Date: 1999-09-16 Impact factor: 49.962
Authors: M Lajemi; S Gautier; O Poirier; J P Baguet; A Mimran; P Gosse; O Hanon; C Labat; F Cambien; A Benetos Journal: Am J Hypertens Date: 2001-08 Impact factor: 2.689
Authors: R Brugada; W Kelsey; M Lechin; G Zhao; Q T Yu; W Zoghbi; M Quinones; E Elstein; A Omran; H Rakowski; D Wigle; C C Liew; M Sole; R Roberts; A J Marian Journal: J Investig Med Date: 1997-12 Impact factor: 2.895