a 2006

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

KAŇKOVÁ, Kateřina; Lukáš PÁCAL; Michal JURAJDA; Petr KOLÁŘ; Lydie IZAKOVIČOVÁ HOLLÁ et al.

Základní údaje

Originální název

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

Název česky

Haplotypová analýza chromosomu 6p zahrnující AGER – TNFA – LTA – NFKBIL1 – BAT1 lokusy: Predběžné výsledky asociační studie u diabetické nefropatie a retinopatie

Vydání

2006

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30202 Endocrinology and metabolism

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14330/06:00015475

Organizační jednotka

Fakulta informatiky

Klíčová slova anglicky

diabetic complications; retinopathy; haplotype

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 2. 4. 2010 15:14, prof. MUDr. Kateřina Kaňková, Ph.D.

Anotace

V originále

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.

Česky

Prace popisuje vysledky srovnavaci studie haplotypovych analyz u diabeticke nefropatie a retinopatie, konkretne SNPs v genech pro AGER a LTA jako varianty zodpovedne za pozorovane rozdily.

Návaznosti

GA310/06/0827, projekt VaV
Název: Genetické determinanty pro-/antioxidační rovnováhy v patogeneze respiračních nemocí
Investor: Grantová agentura ČR, Genetické determinanty pro-/antioxidační rovnováhy v patogeneze respiračních nemocí
KJB501620601, projekt VaV
Název: Funkční analýza rizikového haplotypu RAGE genu a jeho role v patogenezi hyperglykemií indukovaných změn
Investor: Akademie věd ČR, Funkční analýza rizikového haplotypu RAGE genu a jeho role v patogenezi hyperglykemií indukovaných změn