ABSTRACT
BACKGROUND: Headache is common in communities; however, epidemiological research regarding its prevalence is infrequent in India. AIM: We planned to study the prevalence of migraine, its disease burden, and the associated risk factors. SETTING AND DESIGN: This is an urban community study conducted in Kolkata with a cross-sectional and nested case-control design. MATERIALS AND METHODS: The criteria to study headache among a representative sample (aged 20-50 years) was based on the International Classification of Headache Disorders-II. Sex- and age-matched controls without headache were evaluated for putative risk factors. The disease burden was measured as disability adjusted life years (DALY). RESULTS: Screening of 2421 individuals revealed that the 1-year prevalence of migraine was 14.12%. Education, environmental exposure, travel, and oral contraceptives determine approximately 75% of the underlying risks. DALY showed maximum burden among women in the age range of between 30 and 34 years. CONCLUSION: The community-based prevalence of migraine in India is similar to that observed in other countries except Africa. The burden was maximum among women. The risk factors responsible for migraine should be addressed and institution of public health measures are warranted.
Subject(s)
Headache/epidemiology , Headache/therapy , Migraine Disorders/epidemiology , Migraine Disorders/therapy , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , India/epidemiology , Male , Middle Aged , Prevalence , Risk Factors , Young AdultABSTRACT
The aim of this study is to examine the role of GCH1 among Indians affected with dopa responsive dystonia (DRD) and early onset Parkinson's disease (EOPD). The patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were screened for variants in GCH1 by PCR amplification of exons, splice junctions and 1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants (p.Met1Val, p.Val204_205del, IVS3+68A>G, and IVS5-6T>G) were identified in 10 patients but not in the controls. In addition to two nonsynonymous changes, identified in four DRD patients in heterozygous condition, one intronic variant (IVS5-6T>G) could be linked to pathogenesis of the disease since it has the potential of altering the splice site as assessed by in silico analysis. Patients carrying different nonsynonymous variants had remarkable variation in clinical phenotype. Consistent with earlier reports, severity of clinical phenotype and the age of onset varied among family members harboring the same mutation. No mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene have been found and are shown to be associated with variable clinical phenotypes mostly within the spectrum of DRD. The mutations identified represent 15.79% (3/19) of east Indian DRD patient cohort.
Subject(s)
Dystonia/genetics , GTP Cyclohydrolase/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Adult , Asian People/genetics , DNA Mutational Analysis , Dopamine Agents/therapeutic use , Dystonia/drug therapy , Family Health , Female , Humans , India , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/drug therapy , Parkinson Disease/geneticsABSTRACT
Glycogen synthase kinase-3ß (GSK3B) and cyclin-dependent kinase 5 (CDK5) are the 2 major protein kinases involved in abnormal phosphorylation of tau. To determine their potential role in the pathogenesis of Parkinson's disease (PD) we analyzed 2 functional single nucleotide polymorphisms (SNPs) of GSK3B (rs334558 and rs6438552) and rs735555 of CDK5 regulatory subunit 1 (CDK5R1) in 373 PD cases and 346 healthy controls of eastern India. The C,C and T,C haplotypes of GSK3B were respectively moderately associated with increased risk and protection for late onset PD (LOPD) (odds ratio [OR], 1.399; 95% confidence interval [CI], 1.069-1.829; p = 0.015, and OR, 0.436; 95% CI, 0.222-0.853; p = 0.016, respectively). Moreover, moderate to significant interaction between different loci were observed for the entire PD cohort or late onset PD only. However, among these interactions, individuals carrying the (C/C) genotype at both loci (rs6438552 and rs735555) had almost twice the risk of developing PD than those without this genotypic combination (OR, 1.871; 95% CI, 1.181-2.964; p = 0.009). Thus, synergistic effect between the 2 major tau kinases, through these SNPs, appears to determine the risk profile for PD.
Subject(s)
Glycogen Synthase Kinase 3/physiology , Nerve Tissue Proteins/physiology , Parkinson Disease/epidemiology , Parkinson Disease/metabolism , tau Proteins/metabolism , Adult , Cohort Studies , Female , Glycogen Synthase Kinase 3 beta , Humans , India/epidemiology , Male , Middle Aged , Parkinson Disease/genetics , Polymorphism, Single Nucleotide/genetics , Risk Factors , tau Proteins/geneticsABSTRACT
Mutations in PINK1 have been identified in familial and sporadic cases of early onset Parkinson's disease (PD). To determine the contribution of PINK1 variants in Indian PD patients, the gene was screened in 250 patients and 205 ethnically matched controls by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. Two potentially pathogenic variants (Arg246Gln & Arg276Gln) were detected in the heterozygous state in 5 patients; none of the patients carried homozygous or compound heterozygous mutations. In addition, 13 other variants were identified, including a known polymorphism (Ala340Thr), a few synonymous or intronic changes, none of which are likely to be pathogenic. Unlike the Chinese population, the Ala340Thr variant did not show any association with PD in Indian population. Six single nucleotide polymorphisms (SNPs) selected from dbSNP were genotyped in 531 normal, healthy individuals representing different ethnic groups of India. Most of the SNP markers were observed to be highly heterozygous among Indians, which could be used for segregation analysis of PINK1 alleles in familial PD cases.
Subject(s)
Parkinson Disease/genetics , Polymorphism, Genetic/genetics , Protein Kinases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amino Acids/genetics , Animals , Case-Control Studies , Child , DNA Mutational Analysis , Female , Gene Frequency , Humans , India , Linkage Disequilibrium , Male , Middle Aged , Parkinson Disease/physiopathology , Young AdultABSTRACT
Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system and its prevalence increases with age. Microtubule-associated protein tau (MAPT), a neuronal protein is involved in the pathogenesis of several neurodegenerative diseases including PD. To determine the broader significance of this association with PD, replicative studies in distinct ethnic populations are required. In this study, we investigated MAPT for its potential association with PD using five haplotype-tagging SNPs and the del-In9 polymorphism of MAPT in 301 PD patients and 243 healthy controls from eastern India. Our case-control analysis did not show a significant association with any of the markers and PD. However, a risk haplotype [GAC+G] for PD was identified (OR=1.563; 95% CI=1.045-2.337; p=0.03). In addition, haplotype AAC+A (OR=2.787; 95% CI=1.372-5.655; p=0.004) was strongly associated with early onset PD (age at onset < or =40 years) and AAC+G haplotype showed a weak association (OR=2.233; 95% CI=1.018-4.895; p=0.045) with late onset PD (age at onset >40 years). This observation highlights the significance of rs7521 in modifying the age at onset of PD under a common haplotype background. We also identified AGC+A as a risk haplotype for sporadic cases (OR=2.773, 95% CI=1.198-6.407, p=0.016). This is the first association study from India conducted on MAPT among PD patients and provides valuable information for comparison with other ethnic groups.
