title: Renin-angiotensin-aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients.
abstract: BACKGROUND
  The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients.
  
  
  METHODS
  Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP.
  
  
  RESULTS
  Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity.
  
  
  CONCLUSIONS
  Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.
authors.affiliation: University of Monastir, Tunisia.
authors.forename: Nabil
authors.initials: N
authors.lastname: Mtiraoui
authors.forename: Intissar
authors.initials: I
authors.lastname: Ezzidi
authors.forename: Amira
authors.initials: A
authors.lastname: Turki
authors.forename: Molka
authors.initials: M
authors.lastname: Chaieb
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000808:Angiotensinogen / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: C534931:AGT protein, human; D000808:Angiotensinogen