Genetic susceptibility to Parkinson's disease among South and North Indians: I. Role of polymorphisms in dopamine receptor and transporter genes and association of DRD4 120-bp duplication marker.
The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent.
Juyal
Ramesh C
RC
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India. ramesh@nii.res.in
Das
Mitashree
M
Punia
Sohan
S
Behari
Madhuri
M
Nainwal
Geetika
G
Singh
Sumit
S
Swaminath
Pazhayannur V
PV
Govindappa
Shyla T
ST
Jayaram
Sachi
S
Muthane
Uday B
UB
Thelma
B K
BK
D000328:Adult; D000368:Aged; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011954:Receptors, Dopamine / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4