Analysis of three genetic markers in IgA nephropathy patients from a single region.
BACKGROUND
IgA nephropathy (IgA-N) is the most common glomerular disease. Various genetic factors have been suspected to influence the disease, but they never have been studied in the same cohort of patients.


METHODS
In 125 IgA-N biopsy-proven cases, we studied by DNA techniques the allele distribution of 3 polymorphic loci: the angiotensin-converting enzyme (ACE) gene, the specific HLA-DQB1 gene and the hs1,2 enhancer of the alpha1 gene of the IgH locus. Patients were classified as progressive and non-progressive based on a creatininemia above 150 microl/ml or/and a deterioration of the clearance greater than 3 ml/min/year. We analyzed the influence of the polymorphism on the development and the progression of the disease. The control group consisted of 83 heathly subjects.


RESULTS
The frequency of HLA-DQB1*0602 was decreased in IgA-N patients (3.6% vs 10.2%, Pc = 0.04, RR = 0.36), suggesting a protective effect of this allele for IgA-N. Kaplan-Meyer analysis with the Cox-proportional hazard model revealed a shorter time between diagnosis and renal failure in patients with the B allele for the al gene hs1,2 enhancer (p = 0.04). ACE polymorphism did not influence the development or the progression of the disease.


CONCLUSIONS
Genes controlling the immune response, such as HLA DQB1 and the alpha1 transcriptional enhancer gene, may influence the development and/or the progression of IgA-N nephropathy. Patients who develop an IgA-N nephropathy have a higher risk of severe evolution if they have a profile of high IgA humoral responder.
Drouet
M
M
Service d'Immunologie, Faculté de Médecine, Limoges, France. drouet@unilim.fr
Aupetit
C
C
Denizot
Y
Y
Bois
M
M
Bridoux
F
F
Aldigier
J C
JC
Cogné
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D016016:Proportional Hazards Models
D005819:Genetic Markers