title: Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease.
abstract: Idiopathic Parkinson's disease is a common movement disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is postulated to involve complex interactions between genetic susceptibility and environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of human chromosome 11 is a gene rich region expressing several proteins important for dopamine neuron homeostasis. We used a haplotyping approach to determine whether common genetic variation in the IGF2-INS-TH cluster influences the risk of idiopathic Parkinson's disease in a Caucasian case-control group recruited from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689 and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and gender-matched controls. Eight common haplotypes accounted for 91% of the genetic variation in our control group and one haplotype, IGF2-INS-TH*6, was significantly under-represented among the cases with idiopathic Parkinson's disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the individual polymorphisms showed that the IGF2-rs680 alternate 'A' allele accounted for the majority of the protective effect. Our findings suggest that common genetic variants in the IGF2-INS-TH cluster modify susceptibility to idiopathic Parkinson's disease.
authors: School of Biomolecular and Biomedical Sciences, Eskitis Institute, Griffith University, Brisbane, Australia.
authors: Greg
authors: G
authors: Sutherland
authors: George
authors: G
authors: Mellick
authors: Jeremy
authors: J
authors: Newman
authors: Kay L
authors: KL
authors: Double
authors: Julia
authors: J
authors: Stevens
authors: Linda
authors: L
authors: Lee
authors: Dominic
authors: D
authors: Rowe
authors: Peter
authors: P
authors: Silburn
authors: Glenda M
authors: GM
authors: Halliday
mesh_terms: D005838:Genotype; D006239:Haplotypes; D007328:Insulin / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D005810:Multigene Family; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D013963:Thyroid Hormones / Q000235:genetics*
chemical_list: D007328:Insulin; D013963:Thyroid Hormones; D007335:Insulin-Like Growth Factor II