title: Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy.
abstract: An intronic single nucleotide polymorphism (SNP) in the CYP3A5 gene (CYP3A5*3; SNP rs776746) affects RNA splicing and enzymatic activity. The CYP3A5*3 frequency increased with distance from the equator and natural selection has been proposed to explain the worldwide distribution of this allele. CYP3A activity has been related with the risk for hypertension in pregnancy, a major cause of morbidity and mortality among women, and CYP3A5*3 could reduce the risk for this disease in populations from regions with high sodium and water availability. The CYP3A5 genotype was related with blood pressure in the general population, but the effect on the risk for hypertension in pregnancy has not been evaluated.We compared the allele and genotype frequencies of three functional SNPs in the CYP3A5 (rs776746), CYP3A4 (rs2740574), and CYP21A2 (rs6471) genes between pregnant women who developed hypertension (n = 250) or who remained normotensive (control group, n = 250). In addition, we sequenced the full CYP3A5 coding sequence in 40 women from the two groups to determine whether some gene variants could explain the risk for hypertensive pregnancies in our population.Allele and genotype frequencies did not differ between hypertensive and normotensive women for the three CYP variants. We did not find CYP3A5 nucleotide changes that could explain a higher risk for hypertension in pregnancy. Our data suggests that the variation in CYP3A5, CYP3A4, and CYP21A2 did not contribute to the risk for hypertension in pregnancy in our population.
authors.affiliation: Genética Molecular-Red de Investigación Renal (REDINREN)-Fundación Renal, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain. eliecer.coto@sespa.princast.es
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tavira
authors.forename: Rafael
authors.initials: R
authors.lastname: Marín
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
mesh_terms: D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D013030:Spain / Q000453:epidemiology; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; C510163:CYP3A4 protein, human