PMID- 29992511 OWN - NLM STAT- MEDLINE DCOM- 20191016 LR - 20191016 IS - 1559-1174 (Electronic) IS - 1535-1084 (Linking) VI - 20 IP - 3 DP - 2018 Sep TI - Potential Role of Brain-Derived Neurotrophic Factor and Dopamine Receptor D2 Gene Variants as Modifiers for the Susceptibility and Clinical Course of Wilson's Disease. PG - 401-408 LID - 10.1007/s12017-018-8501-2 [doi] AB - Wilson's disease (WD), an inborn error of copper metabolism caused by mutations in the ATPase copper transporting beta (ATP7B) gene, manifests variable age of onset and different degrees of hepatic and neurological disturbances. This complex phenotypical outcome of a classical monogenic disease can possibly be explained by modifier loci regulating the clinical course of the disease. The brain-derived neurotropic factor (BDNF), critical for the survival, morphogenesis, and plasticity of the neurons, and the dopamine receptor D2 (DRD2), one of the most abundant dopamine receptors in the brain, have been highlighted in the pathophysiology of various neuropsychiatric diseases. This study aims to identify the potential association between BDNF and DRD2 gene polymorphisms and WD and its clinical characteristics. A total of 164 WD patients and 270 controls from India were included in this study. Two BDNF polymorphisms [p.Val66Met (c.G196A) and c.C270T] and the DRD2 Taq1A (A2/A1 or C/T) polymorphism were examined for their association with WD and some of its clinical attributes, using polymerase chain reaction, restriction fragment length digestion, and bidirectional sequencing. The C allele and CC genotype of BDNF C270T were significantly overrepresented among controls compared to WD patients. In addition, a significantly higher proportion of the allele coding for Val and the corresponding homozygous genotype of BDNF Val66Met polymorphism was found among WD patients with age of onset later than 10 years. Furthermore, the A1A1 genotype of DRD2 Taq1A polymorphism was significantly more common among WD patients with rigidity. Our data suggest that both BDNF and DRD2 may act as potential modifiers of WD phenotype in the Indian context. FAU - Roy, Shubhrajit AU - Roy S AD - S. N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. FAU - Pal, Prosenjit AU - Pal P AD - S. N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. FAU - Ghosh, Sampurna AU - Ghosh S AD - Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. FAU - Bhattacharya, Sreyashi AU - Bhattacharya S AD - Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. FAU - Das, Shyamal Kumar AU - Das SK AD - Bangur Institute of Neurosciences, Kolkata, India. FAU - Gangopadhyay, Prasanta Kumar AU - Gangopadhyay PK AD - Calcutta National Medical College, Kolkata, India. FAU - Bavdekar, Ashish AU - Bavdekar A AD - KEM Hospital, Pune, India. FAU - Ray, Kunal AU - Ray K AD - Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. FAU - Sengupta, Mainak AU - Sengupta M AUID- ORCID: 0000-0002-4031-1810 AD - Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. sengupta.mainak@gmail.com. FAU - Ray, Jharna AU - Ray J AD - S. N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. jharnaray@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180710 PL - United States TA - Neuromolecular Med JT - Neuromolecular medicine JID - 101135365 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DRD2 protein, human) RN - 0 (Receptors, Dopamine D2) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Adolescent MH - Adult MH - Alleles MH - Brain-Derived Neurotrophic Factor/genetics/*physiology MH - Child MH - Child, Preschool MH - Female MH - Gene Frequency MH - Genotype MH - Hepatolenticular Degeneration/*genetics MH - Humans MH - India MH - Infant MH - Male MH - Polymorphism, Restriction Fragment Length MH - *Polymorphism, Single Nucleotide MH - Receptors, Dopamine D2/genetics/*physiology MH - Young Adult OTO - NOTNLM OT - BDNF OT - DRD2 OT - WD OT - Wilson's disease EDAT- 2018/07/12 06:00 MHDA- 2019/10/17 06:00 CRDT- 2018/07/12 06:00 PHST- 2018/04/06 00:00 [received] PHST- 2018/07/07 00:00 [accepted] PHST- 2018/07/12 06:00 [pubmed] PHST- 2019/10/17 06:00 [medline] PHST- 2018/07/12 06:00 [entrez] AID - 10.1007/s12017-018-8501-2 [pii] AID - 10.1007/s12017-018-8501-2 [doi] PST - ppublish SO - Neuromolecular Med. 2018 Sep;20(3):401-408. doi: 10.1007/s12017-018-8501-2. Epub 2018 Jul 10.