J 2004

Multilocus approach to the identification of genetic risk factors for diabetic nephropathy in type 2 diabetes

KAŇKOVÁ, Kateřina, Miluše HERTLOVÁ, Darja KRUSOVÁ, Susanne SCHWENKE, Jurg OTT et. al.

Basic information

Original name

Multilocus approach to the identification of genetic risk factors for diabetic nephropathy in type 2 diabetes

Name in Czech

Multilokusovy pristup k identifikaci genetickych rizikovych faktoru diabeticke nefropatie u diabetu 2. typu

Authors

KAŇKOVÁ, Kateřina (203 Czech Republic, guarantor), Miluše HERTLOVÁ (203 Czech Republic), Darja KRUSOVÁ (203 Czech Republic), Susanne SCHWENKE (276 Germany) and Jurg OTT (840 United States of America)

Edition

Diabetologia, Germany, Springer Verlag Berlin, 2004, 0012-186X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30202 Endocrinology and metabolism

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.583

RIV identification code

RIV/00216224:14110/04:00010158

Organization unit

Faculty of Medicine

UT WoS

000223951600126

Keywords in English

diabetes; polymorphisms; diabetic nephropathy
Změněno: 23/6/2009 15:22, prof. MUDr. Kateřina Kaňková, Ph.D.

Abstract

V originále

Background and aims: Set association of selected genetic polymorphisms (40 single nucleotide polymorphisms (SNPs)) in 26 candidate genes on chromosomes 1, 3, 4, 6, 7, 12, 16, 17, 19, 20 and 22 with diabetic nephropathy (DN) was studied in patients with type 2 diabetes mellitus. Products of genes studied were components of renin-angiotensin system, other haemodynamic factors, antioxidant enzymes, cytokines and growth factors, AGE-receptors, extracellular matrix remodelation enzymes and others. Materials and methods: A total of 650 unrelated Caucasian subjects were enrolled into study comprising three groups: diabetics with parallel DN (cases), diabetics without DN (controls 1) and non-diabetics (controls 2). DN diagnosis was based on assessment of albumin excretion rate (AER). Genotypes were detected by means of PCR-based methodology. Set association study was performed to find SNPs jointly associated with disease. Results: An initial comparison of genotype frequencies in case and pooled control individuals furnished P-values below 0.05 for 3 SNPs located on the 6th chromosome, namely 2184A/G in the RAGE gene (Receptor of Advanced Glycation End products), 252A/G in the LTA gene (LymphoToxin-Alpha, formely TNFb) and A16V in the SOD2 gene (Mn superoxiddismutase). Comparing each genotype with the other two combined, the strongest frequency differences between cases and controls were observed for genotype RAGE 2184GG and genotype LTA AA (P=0.03 each). Haplotype analysis furnished highly significant (P<0.0001) results. The highest odds ratio for cases versus controls was 3.58, which was observed for haplotype consisting of the following alleles: RAGE -429C/RAGE 2184G/LTA 252A/SOD2 16A. Conclusions: The preliminary data indicate that certain polymorphisms in genes encoding AGE-receptors, antioxidant enzymes and cytokines could be regarded as contributors to genetic risk factors for DN in type 2 diabetes. Association of these polymorphisms with susceptibility to develop DN and rate of progression and severity of DN in type 1 diabetes is a subject of ongoing study.

In Czech

Predbezne vysledky naznacuji, ze vybrane polymorfizmy v genech kodujicich AGE-receptory, antioxidacni enzymy a cytokiny funguji jako rizikove faktory diabeticke nefropatie.

Links

GP303/02/D127, research and development project
Name: Vztah genetické variability antioxidačního systému k pozdním komplikacím diabetu mellitu
Investor: Czech Science Foundation, Relationship between genetic variability of antioxidant system and late complications of diabetes mellitus
MSM 141100002, plan (intention)
Name: Molekulární patofyziologie multigenních chorob
Investor: Ministry of Education, Youth and Sports of the CR, Molecular pathophysiology of multigene diseases