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@article{704945,
author = {Kaňková, Kateřina and Stejskalová, Andrea and Pácal, Lukáš and Tschöplová, Svatava and Hertlová, Miluše and Krusová, Darja and Izakovičová Hollá, Lydie and Beránek, Michal and Vašků, Anna and BarralandRodriguez, Sandra and Ott, Jurg},
article_location = {Germany},
article_number = {5},
keywords = {diabetic nephropathy; endothelin; haplotype; LTA; lymphotoxin A; nitric oxide synthase; NOS3; RAGE; Receptor of Advanced Glycation End products; set-association},
language = {eng},
issn = {0012-186X},
journal = {Diabetologia},
title = {Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach},
volume = {50},
year = {2007}
}
TY - JOUR
ID - 704945
AU - Kaňková, Kateřina - Stejskalová, Andrea - Pácal, Lukáš - Tschöplová, Svatava - Hertlová, Miluše - Krusová, Darja - Izakovičová Hollá, Lydie - Beránek, Michal - Vašků, Anna - Barral-Rodriguez, Sandra - Ott, Jurg
PY - 2007
TI - Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach
JF - Diabetologia
VL - 50
IS - 5
SP - 990-999
EP - 990-999
PB - Springer Verlag Berlin
SN - 0012186X
KW - diabetic nephropathy
KW - endothelin
KW - haplotype
KW - LTA
KW - lymphotoxin A
KW - nitric oxide synthase
KW - NOS3
KW - RAGE
KW - Receptor of Advanced Glycation End products
KW - set-association
N2 - Aims: We studied association of a set of 45 SNPs in 20 candidate genes on 8 chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits - single vs. multilocus analysis. Methods: The study comprised a total of 647 in one of the three groups: diabetics with or without DN or non-diabetics. Genotypes were detected by PCR-based methodology (PCR only, PCR + RFLP or allele-specific PCR). Haplotypes were inferred in silico, Set association (programme SUMSTAT) was used for multilocus analysis. Results: After correction for multiple comparisons, one SNP only - RAGE 2184A/G (AGER gene) - showed a significant association with DN (p=0.0006) in single-locus analysis. In multilocus analysis, six SNPs exhibited significant association with DN: 4 SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A, and AGER -429T/C) and 2 SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p=0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p=0.0002), however, no significant difference in frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression identified SNPs AGER 2184A/G and NOS3 774C/T together with diabetes duration and HbA1c as significant predictors of DN. Finally, testing for interactions between SNPs on chromosomes 6 and 7 did not furnish significant evidence for epistatic interaction. Conclusions: Using set-association approach we identified significant association of several SNPs on chromosomes 6 and 7 with DN. Both approaches - single and multilocus - represent complementary methods.
ER -
KAŇKOVÁ, Kateřina, Andrea STEJSKALOVÁ, Lukáš PÁCAL, Svatava TSCHÖPLOVÁ, Miluše HERTLOVÁ, Darja KRUSOVÁ, Lydie IZAKOVIČOVÁ HOLLÁ, Michal BERÁNEK, Anna VAŠKŮ, Sandra BARRAL-RODRIGUEZ and Jurg OTT. Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. \textit{Diabetologia}. Germany: Springer Verlag Berlin, 2007, vol.~50, No~5, p.~990-999. ISSN~0012-186X.
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