RESUMEN
BACKGROUND & OBJECTIVES: Search for candidate genes for alcohol dependence (AD) has been inconsistent and inconclusive. Moreover, most of the research has been confined to a few specific ethnic groups. Hence, the aim of our study was to explore specific candidate genes for AD in north Indian male population. METHODS: In this clinic-based genetic association study, 210 males with AD and 200 controls matched for age, gender and ethnicity were recruited from the clinic and the general population, respectively. Cases were diagnosed with Semi-structured Assessment for Genetics of Alcoholism-II (SSAGA-II). Single-nucleotide polymorphism genotyping was done by real-time quantitative-polymerase chain reaction (PCR) using Taq Man assay (ABI 7500) fast real-time PCR system. RESULTS: Both at the genotypic level and at allelic frequency, Met158 variant of catechol-O-methyl transferase (COMT) showed significant increase in cases as compared to controls. The frequency of heterozygous genotype (A/G) of gamma-aminobutyric acid receptor A1 (GABRA1) was significantly lower in cases as compared to controls. Likewise, for GABRA2, the frequency of homozygous recessive genotype (G/G) was significantly higher in the control group. With respect to the 5-hydroxytryptamine (5HT) transporter long promoter region (5HTTLPR), cholinergic receptor muscarinic (CHRM2) and alcohol dehydrogenase 1B (ADH1B) genes, there was no significant difference between the cases and the controls. Aldehyde dehydrogenase (ALDH2) gene was found to be monomorphic in our study population. INTERPRETATION & CONCLUSIONS: Our study findings showed COMT polymorphism conferring risk and GABRA polymorphism as a protective genotype for Indian male with AD. Genes for alcohol metabolism, serotonin transporter and cholinergic receptor gene polymorphism were perhaps not contributory to AD for Indian population.
Asunto(s)
Alcoholismo/genética , Catecol O-Metiltransferasa/genética , Receptores de GABA-A/genética , Adulto , Alcohol Deshidrogenasa/genética , Alcoholismo/patología , Aldehído Deshidrogenasa Mitocondrial/genética , Pueblo Asiatico , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Receptor Muscarínico M2/genética , Serotonina/genéticaRESUMEN
INTRODUCTION: Pseudoexfoliation syndrome is commonly associated with pseudoexfoliation glaucoma. The two nonsynonymous single-nucleotide polymorphisms rs1048661 (R141L) and rs3825942 (G153D) within exon 1 of LOXL1 gene have been found to confer risk of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in different geographical populations. This study aims to find association between two nonsynonymous single-nucleotide polymorphisms with pseudoexfoliation syndrome and pseudoexfoliation glaucoma in North Indian population. METHODS: North Indian subjects clinically diagnosed with pseudoexfoliation syndrome/pseudoexfoliation glaucoma and normal age-matched control were enrolled in the study. Genomic DNA was extracted and the two single-nucleotide polymorphisms of LOXL1 gene were genotyped by polymerase chain reaction and sequencing. The association between single-nucleotide polymorphisms with pseudoexfoliation syndrome/pseudoexfoliation glaucoma was evaluated by chi-square test. RESULTS: A total of 30 pseudoexfoliation glaucoma, 27 pseudoexfoliation syndrome and 61 control subjects were enrolled in the study. Patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma did not show any genetic association with either single-nucleotide polymorphism rs1048661 or rs3825942. CONCLUSION: The study shows lack of association between LOXL1 single-nucleotide polymorphisms and pseudoexfoliation in North Indian population.
Asunto(s)
Aminoácido Oxidorreductasas/genética , Síndrome de Exfoliación/genética , Glaucoma de Ángulo Abierto/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Casos y Controles , Síndrome de Exfoliación/diagnóstico , Exones/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Glaucoma de Ángulo Abierto/diagnóstico , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND AND AIMS: Delirium Tremens (DT) is the most severe form of alcohol withdrawal syndrome, with a potential risk of mortality. Search for the predictors of DT led to study of candidate genes, with inconsistent and inconclusive results. This study aimed to explore the association of various candidate gene polymorphisms and DT in a case-control design. METHODS: This was a genetic association study with a case control design. Two hundred ten Alcohol dependent (AD) male subjects and 200 age matched controls were recruited. DT was diagnosed with the help of Semi-structured Assessment for Genetics of Alcoholism. SNP genotyping was done using TaqMan assay by real time PCR (q-PCR). RESULTS: T allele carrying status (GT and TT) [rs1824024] of muscarinic cholinergic receptor 2 (CHRM2) was found to be significantly associated with DT. When compared to the general population, this genetic polymorphism was not found to be more common in alcohol dependence per se, which excludes the possibility of spurious association between CHRM2 and DT. Withdrawal seizure was more common in the DT group and came out to be one of the important predictors of DT. However, the genetic association was found to be specific for DT, not related to withdrawal seizures. CONCLUSION: The present research added a new cholinergic dimension in the genetic association and biological mechanism of DT.