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@proceedings{704946,
author = {Kaňková, Kateřina and Pácal, Lukáš and Jurajda, Michal and Kolář, Petr and Izakovičová Hollá, Lydie},
keywords = {diabetic complications; retinopathy; haplotype},
language = {eng},
title = {Haplotype analysis of the region of 6p chromosome spanning the AGER – TNFA – LTA – NFKBIL1 – BAT1 loci: Preliminary results of association study with diabetic nephropathy and retinopathy},
year = {2006}
}
TY - CONF
ID - 704946
AU - Kaňková, Kateřina - Pácal, Lukáš - Jurajda, Michal - Kolář, Petr - Izakovičová Hollá, Lydie
PY - 2006
TI - Haplotype analysis of the region of 6p chromosome spanning the AGER – TNFA – LTA – NFKBIL1 – BAT1 loci: Preliminary results of association study with diabetic nephropathy and retinopathy
KW - diabetic complications
KW - retinopathy
KW - haplotype
N2 - Aims: Previously we identified RAGE2 haplotype in the AGER gene as a risk factor for diabetic nephropathy (DN) and single nucleotide polymorphism (SNP) 252A/G in the LTA gene as a risk factor for both DN and proliferative diabetic retinopathy (PDR). Recently, multiple SNPs in the BAT1, NFKBIL1 and LTA genes have been found associated with myocardial infarction in the genome-wide association study. Detail analysis of the given MHC III region on chromosome 6p spanning the AGER – TNFA – LTA – NFKBIL1 – BAT1 loci could further elucidate the character of association and help to identify causal variant. The aims of the study were (1) to construct haplotypes based on genotypes of 13 SNPs in the five genes analysed and (2) to ascertain eventual association of ceratin haplotype(s) with DN and/or PDR. Methods: A total of 981 subjects comprising four groups (DM+DN, DM+PDR, DM without complications and non-DM) were included in the study. Genotypes were detected with PCR-based methodology. Haplotypes were inferred in silico using Bayesian algorithm. Differences in haplotype frequencies were tested by permutation testing. After the correction for multiple comparisons Pcorr<0.05 was considered significant. Results: Single locus analysis revealed significant association of the AGER 2184G allele with both DN (23.0% DN vs. 15.2% non-DN, P<0.05) and PDR (23.6% PDR vs. 18.1% non-PDR, P<0.05). Haplotype distribution differed significantly between DN vs. non-DN groups (P<0.05, 10 000 permutations), no significant differences were found for PDR. Haplotypes containing minor alleles in positions AGER 2184 and LTA 252 were more frequent in DN group, similar (yet statistically insignificant) tendency was observed for PDR. Conclusions: Substitutions in AGER and LTA genes are responsible for observed differences in haplotype frequencies and are thus likely to be (or in the close proximity of) causal variants. Functional analysis of both substitutions is warranted.
ER -
KAŇKOVÁ, Kateřina, Lukáš PÁCAL, Michal JURAJDA, Petr KOLÁŘ a Lydie IZAKOVIČOVÁ HOLLÁ. \textit{Haplotype analysis of the region of 6p chromosome spanning the AGER – TNFA – LTA – NFKBIL1 – BAT1 loci: Preliminary results of association study with diabetic nephropathy and retinopathy}. 2006.
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