Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
MH44292
NIMH NIH HHS - United States
- MeSH
- Bayesova věta MeSH
- diabetické nefropatie epidemiologie genetika MeSH
- genotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 6 * MeSH
- lidské chromozomy, pár 7 * MeSH
- mapování chromozomů MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický MeSH
- referenční hodnoty MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
AIMS/HYPOTHESIS: In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight 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- and multi-locus analyses. MATERIALS AND METHODS: The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis. RESULTS: After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two 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, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction. CONCLUSIONS/INTERPRETATION: Using the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods.
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