Emőke Endreffy | University of Szeged (original) (raw)

Papers by Emőke Endreffy

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Abstract Oxidative stress plays an important role in the cardiovascular complications in end-stag... more Abstract Oxidative stress plays an important role in the
cardiovascular complications in end-stage renal disease
(ESRD) patients on long-term hemodialysis (HD). Heme
oxygenase-1 (HO-1) inhibits inflammatory events and
protects against oxidative stress and endothelial injury.
Therefore, we followed the effects of single HD sessions
on HO-1 expression. A competitive reverse transcriptase
PCR method was used to estimate HO-1 induction before
and immediately after HD and 48 h later in 17 young
uremic patients. We also measured the concentrations of
plasma hemoglobin and bilirubin as indicators of hemolysis,
the ferroxidase activity, and the erythrocyte-derived
reduced and oxidized glutathione levels as oxidative
stress markers, and the homocysteine levels as an independent
risk factor. We found significant differences in
HO-1 expression patterns in the patients, depending on
the duration of HD treatment. Short-term HD [n=7,
median 19 months (9, 29 quartiles)] resulted in an
elevated HO-1 expression, which was not further upregulated
during HD. Long-term HD [n=10, median
97 months (53, 150 quartiles)] led to downregulation of
baseline HO-1 expression in ESRD patients. In these
patients, a single HD session results in erythrocyte injury
and a transient one- to five-fold elevation of HO-1
expression. The chronic downregulation of the baseline
expression of HO-1 in long-term HD patients resulted in
recurring oxidative stress during each HD session, which
may contribute to accelerate the progression of atherosclerosis.

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Abstract Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), A... more Abstract
Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger’s syndrome (AS) and pervasive developmental
disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current
study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B12 and the C677T polymorphism
of the MTHFR gene in three groups of children diagnosed with AD (n 15), AS (n 5) and PDD-NOS (n 19) and their ageand
sex-matched controls (n 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups,
lower plasma levels of methionine (P 0.01 and P 0.03, respectively) and -aminobutyrate were observed (P 0.01 and P 0.001,
respectively). Only in the AD group, plasma cysteine (P 0.02) and total blood glutathione (P 0.02) were found to be reduced.
Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these
metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum
levels of vitamin B12 and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the
C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study
indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

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Abstract Oxidative stress is known to play an important role in the pathogenesis of certain sever... more Abstract Oxidative stress is known to play an important
role in the pathogenesis of certain severe illnesses in
preterm infants. The enzyme heme oxygenase-1 (HO-1)
participates in cytoprotection against oxygen radical injury.
We have previously described the role of HO-1 in
physiologic adaptation by demonstrating the induction of
HO-1 in healthy mature neonates and asymptomatic
preterm infants. Our current aim was to investigate the
HO-1 expression in preterm infants with respiratory distress
syndrome (RDS). We collected venous blood samples from
28 preterm infants with RDS on the 1st, 3rd and 5th days
after birth. The HO-1 mRNA expression was determined by
means of a competitive reverse transcriptase PCR technique,
and a quantitative blood count was performed on the
residual blood sample. A significant increase in HO-1
expression was found in the preterm infants with RDS as
compared with both the healthy mature and the asymptomatic
premature groups. The elevation was approximately
eight-fold. The platelet count displayed a significant
negative association with the HO-1 expression, and in the
RDS prematures with thrombocytopenia the HO-1 induction
was significantly greater than in those with a normal
platelet count. In conclusion, the RDS of prematures is
accompanied by an elevated HO-1 expression during the
first 5 days of life, consistent with the inflammatory and
oxidative characteristics of the disease.

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ABSTRACT Objectives To perform fi ne mapping of the autoimmunity susceptibility gene BLK and iden... more ABSTRACT
Objectives To perform fi ne mapping of the autoimmunity
susceptibility gene BLK and identify functional variants
involved in systemic lupus erythematosus (SLE).
Methods Genotyping of 1163 European SLE patients and
1482 controls and imputation were performed covering
the BLK gene with 158 single-nucleotide polymorphisms.
Logistic regression analysis was done using PLINK
and conditional analyses using GENABEL’s test score.
Transfections of BLK constructs on HEK293 cells
containing the novel mutation or the wild type form were
analysed for their effect on protein half-life using a protein
stability assay, cycloheximide and western blot. CHiP-qPCR
for detection of nuclear factor κ B (NFkB) binding.
Results Fine mapping of BLK identifi ed two
independent genetic effects with functional
consequences: one represented by two tightly linked
associated haplotype blocks signifi cantly enriched for
NFκB-binding sites and numerous putative regulatory
variants whose risk alleles correlated with low BLK
mRNA levels. Binding of NFkBp50 and p65 to an
associated 1.2 Kb haplotype segment was confi rmed.
A second independent genetic effect was represented
by an Ala71Thr, low-frequency missense substitution
with an OR=2.31 (95% CI 1.38 to 3.86). The 71Thr
decreased BLK protein half-life.
Conclusions These results show that rare and common
regulatory variants in BLK are involved in disease
susceptibility and both, albeit independently, lead to reduced levels of BLK protein.

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Abstract We targeted LYN, a src-tyosine kinase involved in B cell activation, in case-control ass... more Abstract
We targeted LYN, a src-tyosine kinase involved in B cell activation, in case-control association
studies using populations of European American, African American and Korean subjects. Our
combined European-derived population, consisting of 2463 independent cases and 3131 unrelated
controls, demonstrates significant association with rs6983130 in a female-only analysis with 2254
cases and 2228 controls (p=1.1 × 10−4, OR=0.81 (95% CI: 0.73 – 0.90)). This SNP is located in the
5′ UTR within the first intron near the transcription initiation site of LYN. Additional SNPs upstream
of the first exon also show weak and sporadic association in subsets of the total European American
population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for
SLE susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status
were used as covariates. Subset analysis of the European American female cases by ACR
classification criteria reveals a reduction in the risk of hematologic disorder with rs6983130
compared to cases without hematologic disorders (p=1.5 × 10−3, OR=0.75 (95% C.I.=0.62-0.89)).
None of the 90 SNPs tested demonstrate significant association with SLE in the African American
or Korean populations. These results support an association of LYN with European-derived
individuals with SLE, especially within autoantibody or clinical subsets.

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Introduction We aimed to replicate association of newly identified systemic lupus erythematosus (... more Introduction We aimed to replicate association of newly
identified systemic lupus erythematosus (SLE) loci.
Methods We selected the most associated SNP in 10 SLE loci.
These 10 SNPs were analysed in 1,579 patients with SLE and
1,726 controls of European origin by single-base extension.
Comparison of allele frequencies between cases and controls
was done with the Mantel–Haenszel approach to account for
heterogeneity between sample collections.
Results A previously controversial association with a SNP in the
TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 ×
10-5), as well as association with the X chromosome MECP2
gene (OR = 1.26, P = 0.00085 in women), which had only been
reported in a single study, and association with four other loci,
1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P =
0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR
= 0.84, P = 0.001), which have been identified in a genomewide
association study, but not found in any other study. All
these replications showed the same disease-associated allele
as originally reported. No association was found with the LY9
SNP, which had been reported in a single study.
Conclusions Our results confirm nine SLE loci. For six of them,
TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and
C8orf13-BLK, were already clearly confirmed. Our results also
suggest that MECP2 association has no influence in the sex
bias of SLE, contrary to what has been proposed. In addition,
none of the other associations seems important in this respect.

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