title: HLA-DRB1*03 as a risk factor for microalbuminuria in same duration of type 1 diabetes: a case control study.
abstract: BACKGROUND
  Increased urinary albumin excretion rate is the earliest clinical manifestation of diabetic nephropathy. The development of microalbuminuria in patients with type 1 diabetes mellitus (T1D) usually begins 5 to 15 years after the onset of diabetes. The rate of progression of diabetic nephropathy varies considerably among patients and not always can be explained solely by glycaemic control. The evidence suggests that genetic susceptibility may play a role in the development of diabetes microvascular complications, besides the presence of such risk factors as hyperglycaemia, hypertension, dyslipidaemia and smoking. The aim of the study was to evaluate a link between known genetic risk factors for type 1 diabetes mellitus (HLA-DR3/DR4) and microalbuminuria among patients with the same durations of diabetes.
  
  
  METHODS
  Ninety-nine patients with T1D at the age 18-35 years were recruited for the study. The urine albumin excretion rate was normal when <30 mg/24 h; microalbuminuria 30-300 mg/24 h. Genotypes were investigated in 39 patients with normal albumin excretion rate and duration of diabetes 13.46 ± 3.72 years and in 60 patients with microalbuminuria and duration of diabetes 15.28 ± 4.08 years (p = 0.11). Genetic typing of DR3 and DR4 antigens successfully was performed for 99 subjects. Statistical analysis was performed using SPSS v. 20.0.
  
  
  RESULTS
  Genotyping of 99 patients with T1D was performed: no DR3 and DR4 risk alleles were found in 22 (22.22 %) cases, DR3 alleles were present in 47 (47.48 %) cases, DR4 alleles in 25 (25.25 %) cases, and DR3/DR4 alleles in 5 (5.05 %) cases. The highest 24 h albumin excretion rate was found in patients with DRB1 gene expressed DR3 risk alleles group, the lowest - in patients with DRB1 gene with no expression of both DR3 and DR4 antigen. We confirmed the 1.87 (p = 0.021) increased relative risk for microalbuminuria in patients with DR3/DR3 alleles and same duration of diabetes. The distribution of DR3 and DR4 risk alleles was not associated with cardiovascular autonomic neuropathy both in patients with normal albumin excretion rate and microalbuminuria (1.6 vs 2.1; p = 0.21).
  
  
  CONCLUSIONS
  The 1.87 (p = 0.021) increased relative risk for microalbuminuria was found in patients with DR3/DR3 alleles and the same duration of diabetes.
authors.affiliation: Department of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus 9, Kaunas, LT 44307, Lithuania. dovile.rvirbickiene@gmail.com.
authors.forename: Dovilė
authors.initials: D
authors.lastname: Ražanskaitė-Virbickienė
authors.affiliation: Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania.
authors.forename: Evalda
authors.initials: E
authors.lastname: Danytė
authors.affiliation: Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania.
authors.forename: Rimantas
authors.initials: R
authors.lastname: Žalinkevičius
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen
keywords: AER; Albuminuria; DR3; DR4; HLA; Type 1 diabetes mellitus