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Sökning: onr:"swepub:oai:DiVA.org:liu-114256" > Genetic association...

Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson s disease a multicenter study

von Otter, Malin (författare)
University of Gothenburg, Sweden
Bergström, Petra (författare)
University of Gothenburg, Sweden
Quattrone, Aldo (författare)
Magna Graecia University of Catanzaro, Italy; CNR, Italy
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Valeria De Marco, Elvira (författare)
CNR, Italy
Annesi, Grazia (författare)
CNR, Italy
Söderkvist, Peter (författare)
Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik
Bezzina Wettinger, Stephanie (författare)
University of Malta, Malta
Drozdzik, Marek (författare)
Pomeranian Medical University, Poland
Bialecka, Monika (författare)
Pomeranian Medical University, Poland
Nissbrandt, Hans (författare)
University of Gothenburg, Sweden
Klein, Christine (författare)
Medical University of Lubeck, Germany
Nilsson, Michael (författare)
University of Gothenburg, Sweden; University of Newcastle, Australia
Hammarsten, Ola (författare)
University of Gothenburg, Sweden
Nilsson, Staffan (författare)
Chalmers, Sweden
Zetterberg, Henrik (författare)
University of Gothenburg, Sweden; UCL Institute Neurol, England
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 (creator_code:org_t)
BioMed Central / Springer Verlag (Germany), 2014
2014
Engelska.
Ingår i: BMC Medical Genetics. - : BioMed Central / Springer Verlag (Germany). - 1471-2350 .- 1471-2350. ; 15:131
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: The transcription factor Nrf2, encoded by the NFE2L2 gene, is an important regulator of the cellular protection against oxidative stress. Parkinson s disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of NFE2L2 haplotypes with risk and age at onset of idiopathic Parkinson s disease in a Swedish discovery material and a Polish replication material. Here, we have extended the replication study and performed meta-analyses including the Polish material and four new independent European patient-control materials. Furthermore, all SNPs included in the haplotype windows were investigated individually for associations with Parkinson s disease in meta-analyses including all six materials. Methods: Totally 1038 patients and 1600 control subjects were studied. Based on previous NFE2L2 haplotype associations with Parkinson s disease, five NFE2L2 tag SNPs were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. The impact of individual SNPs and haplotypes on risk and age at onset of Parkinson s disease were investigated in each material individually and in meta-analyses of the obtained results. Results: Meta-analyses of NFE2L2 haplotypes showed association of haplotype GAGCAAAA, including the fully functional promoter haplotype AGC, with decreased risk (OR = 0.8 per allele, p = 0.012) and delayed onset (+ 1.1 years per allele, p = 0.048) of Parkinson s disease. These results support the previously observed protective effect of this haplotype in the first study. Further, meta-analyses of the SNPs included in the haplotypes revealed four NFE2L2 SNPs associated with age at onset of Parkinson s disease (rs7557529 G greater than A, -1.0 years per allele, p = 0.042; rs35652124 A greater than G, -1.1 years per allele, p = 0.045; rs2886161 A greater than G, -1.2 years per allele, p = 0.021; rs1806649 G greater than A, + 1.2 years per allele, p = 0.029). One of these (rs35652124) is a functional SNP located in the NFE2L2 promoter. No individual SNP was associated with risk of Parkinson s disease. Conclusion: Our results support the hypothesis that variation in the NFE2L2 gene, encoding a central protein in the cellular protection against oxidative stress, may contribute to the pathogenesis of Parkinson s disease. Functional studies are now needed to explore these results further.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

Parkinson s disease; PD; Nrf2; NFE2L2; Meta-analysis; Multicenter; SNP; Haplotype; Risk factor

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