title: Genetic determinants of idiopathic noncirrhotic portal hypertension in HIV-infected patients.
abstract: BACKGROUND
  Noncirrhotic portal hypertension (NCPH) is a rare but potentially life-threatening complication in patients with human immunodeficiency virus (HIV). Cases of NCPH have been reported in HIV-negative individuals as result of treatment with thiopurines for leukemia or inflammatory bowel disease. Exposure to didanosine, which is also a purine analogue, predisposes to NCPH in the HIV setting. However, it is unclear why NCPH only develops in a small subset of didanosine-treated patients.
  
  
  METHODS
  A multicenter, case-control study was conducted to investigate the role of pharmacogenomics in NCPH in HIV patients with prior didanosine exposure. Three controls were chosen for each case, adjusted for sex, age, CD4 counts, plasma HIV-RNA, and site. Tagging 36 single-nucleotide polymorphisms (SNPs) at enzymes involved in the purine metabolism (inosine triphosphatase, 5'-nucleotidase cytosolic-II, purine nucleoside phosphorylase and xanthine oxidase) was performed using SNPlex microarray technology.
  
  
  RESULTS
  Eighty individuals were examined; 22 with NCPH and 58 matched controls. Two SNPs at the 5'-nucleotidase gene were associated with NCPH: rs11191561 (48% CG/GG vs 17% CC; P=.003) and rs11598702 (40% CC/CT vs 9% TT; P=.003). SNPs at another 2 loci at the xanthine oxidase gene were also associated with NCPH: rs1429376 (71% AA vs 23% CC/AC; P=.015) and rs1594160 (71% AA vs 23% CC/AC; P=.015). There was a cumulative risk of NCPH for these 4 SNPs: 7%, 26%, 42%, 50%, and 100%, respectively, for 0, 1, 2, 3, or all SNPs (P=.001).
  
  
  CONCLUSIONS
  SNPs at the 5'-nucleotidase and xanthine oxidase genes influence the risk of NCPH in HIV patients treated with didanosine.
authors: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors: Eugenia
authors: E
authors: Vispo
authors: Muge
authors: M
authors: Cevik
authors: Juergen K
authors: JK
authors: Rockstroh
authors: Pablo
authors: P
authors: Barreiro
authors: Mark
authors: M
authors: Nelson
authors: Andrew
authors: A
authors: Scourfield
authors: Christoph
authors: C
authors: Boesecke
authors: Jan-Christian
authors: JC
authors: Wasmuth
authors: Vincent
authors: V
authors: Soriano
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D016049:Didanosine / Q000627:therapeutic use; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D056726:Genetic Association Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D014969:Xanthine Oxidase / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D058851:GPI-Linked Proteins; D014969:Xanthine Oxidase; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D016049:Didanosine