Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease.
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.
Sutherland
Greg
G
School of Biomolecular and Biomedical Sciences, Eskitis Institute, Griffith University, Brisbane, Australia.
Mellick
George
G
Newman
Jeremy
J
Double
Kay L
KL
Stevens
Julia
J
Lee
Linda
L
Rowe
Dominic
D
Silburn
Peter
P
Halliday
Glenda M
GM
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*
D007328:Insulin; D013963:Thyroid Hormones; D007335:Insulin-Like Growth Factor II