Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients.
BACKGROUND
The IL-10 promoter polymorphisms -1082G/A, -819C/T, and -592C/A have been consistently associated with type 2 diabetes (T2DM). We examined whether these polymorphisms variants are also associated with progression of diabetic nephropathy (DN).


METHODS
These promoter variants were genotyped in 917 T2DM patients comprising 515 DN patients and 402 control patients without nephropathy (DWN), together with 748 non-diabetic control subjects. Haplotype analysis and multivariate regression analysis were employed in assessing the contribution of IL-10 haplotypes to DN risk, using genotype, clinical and biochemical profile, and their interactions as predictors of DN.


RESULTS
Carriers of mutant -592A and -819T alleles, and -819T/T, -592A/A, and -819C/T genotypes were more frequent in T2DM. However, the -819C/T genotype appeared to be protective of DN, since lower frequency -819T allele and -819C/T genotype were seen in DN patients. Regression analysis identified -1082G/-819T/-592A (GTA) and -1082G/-819T/-592C (GTC) haplotypes as DN-protective haplotypes. Relative to the -1082G/-819C/-592C haplotype, GTA [P = 0.044; odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30-0.98] and GTC (P = 0.045; OR = 0.56, 95% CI: 0.31-0.99) haplotypes were associated with decreased odds ratio (OR) for DN, after controlling for a number of covariates (age, sex, body mass index (BMI), hypertension, glucose, HbA(1c), DN duration, total cholesterol).


CONCLUSIONS
Our results indicate that genetic variations at the IL-10 promoter influence the risk of nephropathy in T2DM patients and thus represent a potential DN genetic-susceptibility locus worthy of replication.
Mtiraoui
Nabil
N
Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune Diseases, Faculty of Pharmacy of Monastir, Monastir University, Monastir, Tunisia.
Ezzidi
Intissar
I
Kacem
Maha
M
Ben Hadj Mohamed
Manel
M
Chaieb
Molka
M
Haj Jilani
Aoutef Bel
AB
Mahjoub
Touhami
T
Almawi
Wassim Y
WY
D000368:Aged; D018912:Arabs / Q000235:genetics; D003404:Creatinine / Q000097:blood; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014416:Tunisia
D017931:DNA Primers; D007004:Hypoglycemic Agents; D016753:Interleukin-10; D003404:Creatinine