Association of polymorphisms in IL6 gene promoter region with type 1 diabetes and increased albumin-to-creatinine ratio.
BACKGROUND
Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been considered as key factors in type 1 diabetes mellitus (T1DM) and diabetic nephropathy, thus, our aim was to investigate the association of IL6-174G>C (rs1800795) and -634C>G (rs1800796) polymorphisms with T1DM susceptibility and diabetic nephropathy.


METHODS
These polymorphisms were analyzed in 144 children and adolescents with T1DM and 173 normoglycemic control subjects. Glycemic control, laboratory parameters of kidney function and serum lipids were evaluated. By studying only T1DM patients, we evaluated the polymorphisms associated with relevant biochemical parameters in various genetic models.


RESULTS
Type 1 diabetes mellitus patients showed poor glycemic control and albumin-to-creatinine ratio, total cholesterol and LDL-cholesterol levels increased when compared with normoglycemic subjects (p < 0.001, p = 0.004 and p < 0.001, respectively). IL6-174C allele was associated with an increased risk of developing T1DM (OR = 1.53, CI = 1.01-2.31, p = 0.044). In the T1DM group, IL6-174CC carriers showed higher concentrations of glycated hemoglobin (p = 0.029), albumin-to-creatinine ratio (p = 0.021), total cholesterol (p = 0.010), and LDL-cholesterol (p = 0.002), when compared with GG+GC carriers. No association was found for the IL6-634C>G polymorphism.


CONCLUSIONS
These results suggest that IL6-174G>C may contribute to T1DM and increased albumin-to-creatinine ratio as well as to poor glycemic control and hyperlipidemia.
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Marcela Abbott Galvão
MA
Ururahy
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Karla Simone Costa
KS
de Souza
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Yonara Monique da Costa
YM
Oliveira
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Melina Bezerra
MB
Loureiro
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Heglayne Pereira Vital
HP
da Silva
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59072970, Brazil.
Francisco Paulo
FP
Freire-Neto
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
João Felipe
JF
Bezerra
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
André Ducati
AD
Luchessi
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Sonia Quateli
SQ
Doi
Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, 05508900, Brazil.
Rosario Dominguez Crespo
RD
Hirata
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Maria das Graças
Md
Almeida
Department of Pediatrics, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Ricardo Fernando
RF
Arrais
Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, 05508900, Brazil.
Mario Hiroyuki
MH
Hirata
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012570, Brazil.
Adriana Augusto
AA
de Rezende
D000293:Adolescent; D000419:Albuminuria / Q000235:genetics* / Q000652:urine; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D003404:Creatinine; D006442:Glycated Hemoglobin; D015850:Interleukin-6; D014280:Triglycerides; C508600:IL6 protein, human; C517652:hemoglobin A1c protein, human
IL-6; diabetic nephropathy; polymorphism; type 1 diabetes