title: Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1 R and ecNOS.
abstract: BACKGROUND
  Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention.
  
  
  METHODS
  In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control.
  
  
  RESULTS
  The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation.
  
  
  CONCLUSIONS
  This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.
authors.affiliation: Nephrology, Dialysis and Renal Transplantation Department, Hĵpital Nord, CHU de Saint-Etienne, France.
authors.forename: El-Essawy A
authors.initials: el-EA
authors.lastname: Basset
authors.forename: P
authors.initials: P
authors.lastname: Berthoux
authors.forename: S
authors.initials: S
authors.lastname: Cécillon
authors.forename: C
authors.initials: C
authors.lastname: Deprle
authors.forename: D
authors.initials: D
authors.lastname: Thibaudin
authors.forename: J P
authors.initials: JP
authors.lastname: De Filippis
authors.forename: E
authors.initials: E
authors.lastname: Alamartin
authors.forename: F
authors.initials: F
authors.lastname: Berthou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006085:Graft Survival; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A