2007
Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach
KAŇKOVÁ, Kateřina, Andrea STEJSKALOVÁ, Lukáš PÁCAL, Svatava TSCHÖPLOVÁ, Miluše HERTLOVÁ et. al.Základní údaje
Originální název
Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach
Název česky
Identifikace genetických rizikových faktorů pro diabetickou nefropatii na chromozomech 6p a 7q pomocí set-association metody
Autoři
KAŇKOVÁ, Kateřina (203 Česká republika, garant), Andrea STEJSKALOVÁ (203 Česká republika), Lukáš PÁCAL (203 Česká republika), Svatava TSCHÖPLOVÁ (203 Česká republika), Miluše HERTLOVÁ (203 Česká republika), Darja KRUSOVÁ (203 Česká republika), Lydie IZAKOVIČOVÁ HOLLÁ (203 Česká republika), Michal BERÁNEK (203 Česká republika), Anna VAŠKŮ (203 Česká republika), Sandra BARRAL-RODRIGUEZ (840 Spojené státy) a Jurg OTT (840 Spojené státy)
Vydání
Diabetologia, Germany, Springer Verlag Berlin, 2007, 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: 5.822
Kód RIV
RIV/00216224:14110/07:00020074
Organizační jednotka
Lékařská fakulta
UT WoS
000245521400014
Klíčová slova anglicky
diabetic nephropathy; endothelin; haplotype; LTA; lymphotoxin A; nitric oxide synthase; NOS3; RAGE; Receptor of Advanced Glycation End products; set-association
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 23. 6. 2009 09:24, prof. MUDr. Kateřina Kaňková, Ph.D.
V originále
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.
Česky
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.
Návaznosti
| GA310/06/0827, projekt VaV |
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| GP303/02/D127, projekt VaV |
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| GP303/05/P523, projekt VaV |
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| MSM 141100002, záměr |
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