Dopamine β hydroxylase (DBH) polymorphisms do not contribute towards the clinical course of Wilson's disease in Indian patients.

Background: Wilson's disease (WD) is a rare copper metabolism disorder with hepatic and neurological symptoms. Dopamine β hydroxylase (DBH) encodes a copper-dependent mono-oxygenase that converts dopamine to norepinephrine, thereby regulating the endogenous dopamine content in the neurons. Polymorphisms of DBH have been reported to be associated with several neurological diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia and attention-deficit hyperactivity disorder, which have overlapping neurological symptoms with WD.

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.

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.

Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease.

Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests diverse neurological and hepatic phenotypes and different age of onset, even among the siblings, with same mutational background suggesting complex nature of the disease and involvement of other candidate genes. In that context, Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be potential candidates for modifying the WD phenotype and age of onset.

Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation.

Wilson disease (WD) is caused by defects in ATP7B gene due to impairment of normal function of the copper transporting P-type ATPase. This study describes a comprehensive genetic analysis of 199 Indian WD patients including mutations detected in our previous studies, undertakes functional assessment of the nucleotide variants in ATP7B promoter and correlates genotype with disease phenotype. The patient cohort harbors a total of 10 common and 48 rare mutations in the coding region of ATP7B including 21 novel changes.

Systemic infection and inflammation as trigger factors of ischemic stroke.

Background: Chronic risk factors are well understood in cases of stroke as well as myocardial infarction. Till date, several triggers for stroke are still under evaluation. Researchers have previously evaluated the relationship between preceding infection and inflammation and stroke onset.

An association analysis of reelin gene (RELN) polymorphisms with childhood epilepsy in eastern Indian population from West Bengal.

Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early brain developmental abnormalities involving neuronal migration and lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling molecule plays a crucial role in these migratory processes.

Single-nucleotide polymorphism (A118G) in exon 1 of OPRM1 gene causes alteration in downstream signaling by mu-opioid receptor and may contribute to the genetic risk for addiction.

The opioid receptor mu1 (OPRM1) mediates the action of morphine. Although genetic background plays an important role in the susceptibility toward abuse of drugs as evident from familial, adoption and twin studies, association of specific single-nucleotide polymorphisms of OPRM1 gene with narcotic addiction is to be established. Here, we demonstrate the involvement of A118G polymorphism of exon1 of human OPRM1 gene (hOPRM1), with heroin and alcohol addiction, in a population in eastern India.

Reduced NADH coenzyme Q dehydrogenase activity in platelets of Parkinson's disease, but not Parkinson plus patients, from an Indian population.

The observation of decline in mitochondrial electron transport chain function, specifically at complex I, in patients with Parkinson's disease (PD) has been reported by several groups. This study investigates whether a defect of mitochondrial function is present in the platelets of PD patients from an Indian population. We found that the NADH dehydrogenase activity in the platelets of PD patients is lower than that in healthy age- and gender-matched controls, while the succinate dehydrogenase activity was similar in both groups.

Population-based association study and contrasting linkage disequilibrium pattern reveal genetic association of SLC6A4 with autism in the Indian population from West Bengal.

Serotoninergic dysfunction is highly implicated in autism. Serotonin transporter gene (SLC6A4) that regulates synaptic serotonin level has been investigated as a candidate gene for autism, but consensus opinion on possible association is still lacking. Converging evidences of platelet-hyperserotoninemia in approximately 25% of the patients, betterment of ritualistic behavior on administration of SSRI and linkage to chromosome 17q11 harboring SLC6A4, supports the hypothesis that SLC6A4 polymorphisms may contribute towards autism pathology.

Molecular pathogenesis of Wilson disease among Indians: a perspective on mutation spectrum in ATP7B gene, prevalent defects, clinical heterogeneity and implication towards diagnosis.

Aims: We aim to identify the molecular defects in the ATP7B, the causal gene for Wilson disease (WD), in eastern Indian patients and attempt to assess the overall mutation spectrum in India for detection of mutant allele for diagnostic purposes.

Methods: Patients from 109 unrelated families and their first-degree relatives comprising 400 individuals were enrolled in this study as part of an ongoing project. Genomic DNA was prepared from the peripheral blood of Indian WD patients.

Molecular diagnosis of Wilson disease using prevalent mutations and informative single-nucleotide polymorphism markers.

Background: Wilson disease (WD) is an autosomal recessive disorder caused by defects in the ATPase, Cu(2+) transporting, beta-polypeptide gene (ATP7B) resulting in accumulation of copper in liver and brain. WD can be thwarted if detected at a presymptomatic stage, but occasional recombination during carrier detection with dinucleotide repeat markers flanking the WD locus may lead to faulty diagnosis. We examined the use of intragenic single-nucleotide polymorphism (SNP) markers to avoid this limitation.

Reelin gene polymorphisms in the Indian population: a possible paternal 5'UTR-CGG-repeat-allele effect on autism.

Autism is a neurodevelopmental disorder with high heritability factor and the reelin gene, which codes for an extracellular matrix protein involved with neuronal migration and lamination is being investigated as a positional and functional candidate gene for autism. It is located on chromosome 7q22 within the autism susceptible locus (AUTS1); identified in earlier genome scans and several investigations have been carried out on various ethnic groups to assess possible association and linkage of the gene with autism. However, the findings are still inconclusive.

Serotonin transporter promoter variants: Analysis in Indian autistic and control population.

Serotonin transporter (5-HTT) is a transmembrane protein belonging to Na+/Cl- dependent membrane transporter family and transports 5-HT across the membranes of presynaptic neurons. 5-HTT-linked polymorphic region (5-HTTLPR) gained much interest because of the differential regulation of expression and activity of 5-HTT by its various genotypes. A population-based study has been conducted on 5-HTTLPR with 358 individuals, which included 79 autistic probands, 136 parents, and 143 controls from two subpopulations of east and northeast regions of India.

A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD).

Serotonin transporter (SLC6A4) polymorphisms are variously implicated in mediating susceptibility to attention-deficit-hyperactivity disorder (ADHD), a highly heritable and heterogeneous disorder with onset in childhood. Since there has been no survey in this regard from India, a sample of 56 ADHD cases and 174 healthy individuals from Kolkata were genotyped for the SLC6A4 promoter (5-HTTLPR) and intron-2 (STin2) polymorphisms. We report that the observed distribution of allele frequencies is consonant with that expected as per Hardy-Weinberg equilibrium proportions.

Acute intranigral homocysteine administration produces stereotypic behavioral changes and striatal dopamine depletion in Sprague-Dawley rats.

Homocysteine has been considered a major risk factor for cardiovascular diseases, and patients with hyperhomocystinemia exhibit neurological and psychological abnormalities. Elevated level of this molecule in the blood of Parkinson's disease patients receiving long-term l-DOPA therapy prompted us to investigate whether homocysteine is neurotoxic to the nigrostriatal dopaminergic system in Sprague-Dawley rats. Animals infused unilaterally with different doses of homocysteine (0.

Cystathionine beta-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children.

Background: Cystathionine beta-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups.

Methods: The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR.

Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population.

Attention deficit hyperactivity disorder (ADHD) is a childhood onset neurobehavioral disorder. Several studies worldwide have implicated a possible association between ADHD and transmission of different polymorphisms of the dopamine D4 receptor gene (DRD4) in different ethnic groups. However, this is the first report on the transmission of different polymorphisms of DRD4 in Indian subjects.

Molecular aspects of Down syndrome.

Molecular aspects of Down syndrome (DS), a major genetic cause for mental retardation, commonly associated with trisomy 21 are discussed. Two different hypotheses have been speculated to better understand the disease. One believes that increased gene dosage contributes to the phenotypic abnormalities; the other correlates genetic imbalance with DS pathogenesis.

Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children.

Objective: To study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases.

Subjects: Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners Parents and Teachers Rating Scale and Wechslers Intelligence Scale for Children.

Methods: Genomic DNA was amplified for exon 2 *444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis.

Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India.

To identify the genetic modifier(s) that might alter the age at onset in Huntington's disease (HD) we have analyzed variations in GluR6 kainate receptor (GluR6), CA150 gene, Delta2642 and polymorphic CCG repeat variation in huntingtin (htt) gene in 77 HD patients and normal individuals. In addition, variation in the RAI1 gene was analyzed in 30 spinocerebellar ataxia (SCA2) patients and normal individuals to show the possible influence on the age at onset. Multiple regression analysis indicated that variation in GluR6 and CCG repeat genotype might explain 6.