Kinesin light chain 1 gene haplotypes in three conformational diseases

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 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 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.