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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

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An Erratum to this article was published on 30 November 2007

An Erratum to this article was published on 30 November 2007

Abstract

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.

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Acknowledgements

The valuable suggestions and comments on this manuscript by Dr. P. Heutink, Department of Clinical Genetics, Medical Genomics section, VU Medical Center, Amsterdam, are deeply appreciated. The technical assistance of Mohini Khare, Chandini and Kuljeet is acknowledged. Patients and controls, for their valuable participation in the study, and financial assistance through grants from the Department of Science and Technology (grant SP/SO/B-55/2000) and the Department of Biotechnology (grant BT/PR2425/Med/13/089/2001), Govt of India, to RCJ, BKT, MB and UM), New Delhi, India and a senior research fellowship to SP from the University Grants Commission, New Delhi are gratefully acknowledged.

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Authors and Affiliations

  1. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India

    Ramesh C. Juyal, Mitashree Das & Geetika Nainwal

  2. Department of Genetics, University of Delhi South Campus, New Delhi, India

    Sohan Punia & B. K Thelma

  3. Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

    Madhuri Behari & Sumit Singh

  4. Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India

    Pazhayannur V. Swaminath, Shyla T. Govindappa, Sachi Jayaram & Uday B. Muthane

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  1. Ramesh C. Juyal
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Correspondence to Ramesh C. Juyal.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10048-007-0108-y

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Juyal, R.C., Das, M., Punia, S. et al. 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. Neurogenetics 7, 223–229 (2006). https://doi.org/10.1007/s10048-006-0048-y

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