NeuroMolecular Medicine

, Volume 12, Issue 3, pp 229–236

Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases

  • Malin von Otter
  • Sara Landgren
  • Staffan Nilsson
  • Caroline Lundvall
  • Lennart Minthon
  • Nenad Bogdanovic
  • Niels Andreasen
  • Deborah R. Gustafson
  • Ingmar Skoog
  • Anders Wallin
  • Anna Håkansson
  • Hans Nissbrandt
  • Madeleine Zetterberg
  • Gunnar Tasa
  • Kaj Blennow
  • Henrik Zetterberg
Original Paper

Abstract

A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson’s disease (PD), Alzheimer’s disease (AD) and age-related cataract. This case–control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (Pc = 0.04 and Pc = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (Pc = 0.0007 and Pc = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.

Keywords

Parkinson’s disease Alzheimer’s disease Cataract Kinesin KLC1 SNP Haplotype 

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Malin von Otter
    • 1
  • Sara Landgren
    • 2
  • Staffan Nilsson
    • 3
  • Caroline Lundvall
    • 1
  • Lennart Minthon
    • 4
  • Nenad Bogdanovic
    • 5
  • Niels Andreasen
    • 5
  • Deborah R. Gustafson
    • 1
  • Ingmar Skoog
    • 1
  • Anders Wallin
    • 1
  • Anna Håkansson
    • 2
  • Hans Nissbrandt
    • 2
  • Madeleine Zetterberg
    • 6
  • Gunnar Tasa
    • 7
  • Kaj Blennow
    • 1
  • Henrik Zetterberg
    • 1
  1. 1.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at University of GothenburgGothenburgSweden
  2. 2.Department of Pharmacology, Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at University of GothenburgGothenburgSweden
  3. 3.Department of Mathematical Statistics, Institute of Mathematical SciencesChalmers University of TechnologyGothenburgSweden
  4. 4.Department of Clinical Sciences in Malmö, Clinical Memory Research UnitLund UniversityLundSweden
  5. 5.Karolinska Institutet Alzheimer Disease Research Center, Department of NVSKarolinska InstitutetStockholmSweden
  6. 6.Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at University of GothenburgMölndalSweden
  7. 7.Department of Human Biology and Genetics, Institute of General and Molecular PathologyUniversity of TartuTartuEstonia

Personalised recommendations