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.

Základní údaje

Originální název

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

Název česky

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

Autoři

KAŇKOVÁ, Kateřina; Miluše HERTLOVÁ; Darja KRUSOVÁ; Susanne SCHWENKE a Jurg OTT

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30202 Endocrinology and metabolism

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.583

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/04:00010158

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

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

Anotace

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.

Česky

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

Návaznosti

GP303/02/D127, projekt VaV
Název: Vztah genetické variability antioxidačního systému k pozdním komplikacím diabetu mellitu
Investor: Grantová agentura ČR, Vztah genetické variability antioxidačního systému k pozdním komplikacím diabetu mellitu
MSM 141100002, záměr
Název: Molekulární patofyziologie multigenních chorob
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Molekulární patofyziologie multigenních chorob