Sex and body mass index specific regulation of blood pressure by CYP19A1 gene variants.
Sexual dimorphism in blood pressure (BP) regulation has been observed both in humans and experimental animals, and estrogens have been shown to contribute to this epidemiological observation. A key enzyme in determining estrogen levels is aromatase cytochrome P450. The aim of this study was to evaluate the role of the gene encoding aromatase, CYP19A1, as an independent risk factor for hypertension and its relationship with systolic and diastolic BP measures. We genotyped 2 polymorphisms within the CYP19A1 gene, IVS4 rs11575899 and 3'UTR rs10046, in 3448 individuals. In quantitative analysis, we observed significant associations between the 2 polymorphisms and BP values in women, being these associations dependent on BMI and independent of menopause status. The case-control analysis revealed that the most prominent associations were found for nonobese women in diastolic hypertension (DHT): the IVS4_22 and 3'UTR_11 are risk genotypes (OR=1.61, P=0.027 and OR=1.59, P=0.012, respectively), whereas IVS4_11 and 3'UTR_22 genotypes have a protective effect against DHT (OR=0.63, P=0.009, and OR=0.61, P=0.020, respectively). Haplotype analysis confirmed the above associations: among nonobese women the haplotype 21 is overrepresented in hypertensive women (OR=1.33, P=0.004, for DHT and OR=1.25, P=0.026, for systolic hypertension, SHT) and, conversely, the haplotype 12 protects against hypertension (OR=0.78, P=0.015 for DHT and OR=0.82, P=0.04 for SHT). Our study has shown that the CYP19A1 gene may be involved in the genetic regulation of BP in women. This effect is dependent on BMI and independent of menopause status, suggesting that this action is mainly driven by aromatase activity in fat tissue.
Ramirez-Lorca
Reposo
R
Departamento de Genómica Estructural, Neocodex, Parque Tecnológico Isla de la Cartuja, Sevilla, Spain. rrl@neocodex.es
Grilo
Antonio
A
Martinez-Larrad
Maria Teresa
MT
Manzano
Luis
L
Serrano-Hernando
Francisco Javier
FJ
Moron
Francisco Jesus
FJ
Perez-Gonzalez
Vicente
V
Gonzalez-Sanchez
Jose Luis
JL
Fresneda
Javier
J
Fernandez-Parrilla
Rosario
R
Moñux
Guillermo
G
Molero
Eva
E
Sanchez
Elena
E
Martinez-Calatrava
Maria Jose
MJ
Saban-Ruiz
Jose
J
Ruiz
Agustin
A
Saez
Maria Eugenia
ME
Serrano-Rios
Manuel
M
D020413:3' Untranslated Regions; D001141:Aromatase / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D012727:Sex Characteristics; D017678:Sex Distribution; D013030:Spain / Q000453:epidemiology
D020413:3' Untranslated Regions; D001141:Aromatase