Polymorphism of ACE gene as the genetic predisposition of coronary artery disease in Eastern India.

AIM: A case control study was designed to assess whether the prevalence of ACE gene polymorphism has any role in the development of CAD. METHODS: The study included unrelated 217 cases with CAD and 255 healthy controls. PCR was done using primers followed by agarose gel electrophoresis for study of different ACE gene polymorphisms. Multiple logistic regression analysis was carried out to find association between studied genotypes and lifestyle as well as biochemical risk factors. RESULTS: Both DD [OR: 2.16; 95%CI: (60.60-67.40)] and ID [OR: 1.48; 95%CI: (93.28-97.72)] genotypes of the ACE gene showed significant associations in the development of CAD. Coexistence of diabetes and hypertension found to be risk modifier of the disease. Tobacco intake in various forms elevates the risk of the disease among the cases with risk genotypes. CONCLUSION: ID and DD genotypes of ACE gene came out to be predisposing factors for the CAD cases in our study population.

Incidence of anaemia among the female tea garden workers in a tea plantation in upper Assam, India.

Nutritional anaemia is the most common type and cause of anaemia. Tea garden workers constitute approximately 1/5th of population in the state of Assam. Reports indicate higher prevalence of undernutrition in this population. The present study was designed to focus on the incidence of anaemia among the female tea garden workers and to examine the effect of iron with vitamin B12 and folic acid supplementation in them. Two hundred and forty-four female tea garden workers who could be persuaded to participate in the study were sampled for haemoglobin typing by agarose gel electrophoresis (pH 8.9). Their haematological parameters were measured on automated cell counter to read Hb, RBC, MCV, MCH and MCHC. BMI was calculated from weight/height in metre2. The study revealed 182 anaemic (<11.0 g/dl) subjects which included 32 cases of hereditary anaemia and 150 cases of nutritional anaemia. Iron supplementation for duration of 3 months was given to 150 workers out of total 182 subjects who had haemoglobin <11.0 g/dl. Thirteen subjects with haemoglobin >11.0 g/dl were studied as controls. Level of haemoglobin was rechecked after 3 months by Sahli's method. Based on the size of red blood cells it was observed that the workers suffered from all three forms of anaemia viz, microcytic, normocytic and macrocytic. There was a significant rise in haemoglobin concentration when the anaemic individuals took iron with vitamin B12 and folic acid supplement for three consecutive months supported by two doses of anthelminthic drug. The present study showed that nutritional anaemia is a major problem in the female tea garden workers and arrangement of supplementation therapy is utmost necessary to improve their general condition and work efficiency.

Polymorphisms of methylenetetrahydrofolate reductase gene as the genetic predispositions of coronary artery diseases in eastern India.

BACKGROUND: Gene-environment interaction is an important aspect in the development of coronary artery disease (CAD). The mutation (677C-T) of methylenetetrahydrofolate reductase (MTHFR) gene results in a decrease of the enzyme activity that leads to mild hyperhomocysteinemia. Elevated plasma level of homocysteine has been recognized as an independent risk factor for cardiovascular disease. A case-control study was designed to assess whether the prevalence of some MTHFR gene polymorphisms have any role in the development of CAD. MATERIALS AND METHODS: The study included unrelated 217 cases with CAD and 255 healthy controls. DNA was extracted from peripheral blood. MTHFR genotypes were identified by seeing the presence or absence of 677C→T mutation obtained by PCR followed by Hinf1 restriction digestion. Multiple logistic regression analysis was carried out to find association between studied genotypes and lifestyle as well as biochemical risk factors. RESULTS: The T allele was found to be associated with the disease. Significant associations were found with smoking, hypertension, diabetes, and family history of CAD. CONCLUSION: The results indicate that MTHFR 677C-T polymorphism has significant association with CADs in the population of eastern India.

Polymorphisms of CYP1A1, GSTM1 and GSTT1 Loci as the Genetic Predispositions of Oral Cancers and Other Oral Pathologies: Tobacco and Alcohol as Risk Modifiers.

Polycyclic aromatic hydrocarbons of tobacco require activation by phase I enzymes, such as cytochrome-P4501A1 (CYP1A1) to become an ultimate carcinogen, which are subjected to detoxification by phase II enzymes, especially glutathione S-transferases (GSTs). A study was designed to find whether genetic predisposition are risk modifiers of oral pathologies. The study included 102 cases with Oral Cancers (OCs), 68 cases with nonmalignant pathologies, 100 cases as control group. GSTM1 null genotype was associated with increased risk of OCs but not with benign pathologies. Deleted GSTT1 was associated with all pathologies. Both m1m2 and m2m2 polymorphisms of CYP1A1 were associated with oral pathologies.

Cytogenetic monitoring in human oral cancers and other oral pathology: the micronucleus test in exfoliated buccal cells.

Oral cancer is a lifestyle-related cancer, with tobacco as a primary factor. Progression of oral cancer develops over several years from the stage of leukoplakia, erythroplakia, etc. A micronucleus test was applied to oral mucosal cells, considering them as the target site for carcinogens and cytogenetic damage. The test has been established as a reliable biomarker for differential prevalence of MN indices among oral cancers, pre-cancers, non-malignant oral pathologies, and healthy controls for the first time. Buccal scrapings were collected from 63 patients with cancer and pre-cancerous lesions, 42 with non-malignant oral problems, and 100 healthy controls. The analysis revealed that MN frequencies in cancer and pre-cancerous cases were 4-fold elevated (p < 0.001) and 3.87-fold (p < 0.002) elevated for other non-malignant pathologies. Significant associations between use of tobacco in various forms and development of oral pathologies are also established. The relative cancer risk for smoking healthy controls with a definite MN frequency was also found to be significant. The results indicate the validity of the MN test as a cytogenetic marker for the development of several oral pathologies.

Prevalence of CYP1A1 and GST polymorphisms in the population of northeastern India and susceptibility of oral cancer.

Individual cancer susceptibility is the result of several host factors, including differences in lifestyle habits and genetic susceptibility. There is a correlation between CYP1A1 polymorphism (MspI) and oral cancer susceptibility. Individuals carrying the deletions of GSTM1 and GSTT1 are at high risk of developing oral cancers. In the present study on healthy tribal and nontribal individuals of Assam, we found that the genetic variation of GSST polymorphisms is evident (p = 0.20) with differential dose of toxic exposure. Prevalence of different polymorphic alleles of CYP1A1 also proves the same result. A mini-case-control study with very small sample size showed no marked increase in the risk of developing oral cancer as the frequencies of the studied GST genotypes did not show any statistical significance. But GSTT1-null genotypes were found to have higher risk of developing leukoplakia (OR 1.94, 95% CI 2.61-18.54). CYP1A1 genotype m2 allele was also not found to be associated with the risk of developing leukoplakias in the population.

Anemia and hemoglobinopathies in tribal population of Eastern and North-eastern India.

It is estimated that out of approximately 31.4 million people living in North-eastern India, about 8.1 million are tribal people of the hills and plains. Among four of the seven north-eastern states, tribal people are in majority. Arunachal Pradesh is made of approximately 24 major tribal groups, which constitute about 70% of the total population, Tripura 29% and in Assam constitutes 11%. A total of 1726 cases were randomly selected in this study, out of which 1263 cases were from North-east India, namely from Arunachal Pradesh, Assam, Tripura and the rest were from West Bengal. Hematological parameters were estimated and agarose gel electrophoresis for identification of the Hb variants was performed. DNA was isolated, amplified and analysed by PCR-ARMS technology. The incidence of anemia among the tribal people of Assam was 59.82%, in Arunachal Pradesh 53.77% and Tripura 57.45%. The presence of hemoglobinopathies and thalassemia account for anemia in a sizeable population of the north-eastern states in certain tribes and urgent health resources are needed to deal with this. HbE appears to be the commonest hemoglobin among the different tribes of north-east.

Alpha-thalassemia among tribal populations of Eastern India.

Five hundred and thirteen unrelated subjects belonging to various tribes of West Bengal, Arunachal Pradesh and Assam in Eastern India, were screened for the presence of alpha-thalassemia (thal) gene deletion(s) as a possible cause of unexplained anemia (Hb < 11 g/dL and/or MCH <28 pg, MCV < 78 fL). As reported earlier, beta-globin gene mutant alleles were found with a frequency of up to 20% in some tribes. In the present study, alpha-globin gene deletion alleles were found in 18% of subjects from West Bengal, 3.9% from Arunachal Pradesh and 3.84% from Assam tribesmen. Coexistence of alpha- and beta-globin gene abnormalities was observed in up to 18% of some tribal groups. The high inbreeding rate and lack of appropriate medical care make these populations particularly vulnerable.

Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation.

Analysis of the molecular basis of hemoglobinopathies provides an opportunity to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases referred to the counseling unit and 889 individuals from random screening of the population of Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by the PCR-ARMS method using genomic DNA. The haplotype of 56 beta(E) mutation-bearing chromosomes were identified by the RFLP-PCR method. Genotypes were constructed and correlated with hematological and clinical phenotypes. IVS-1nt 5 (G-->C) mutation was observed as the most frequent mutation, followed by codon 30 (G-->C). Production of HbE was significantly (P < 0.001) higher in nontransfusion-dependent Ebeta-thalassemia patients. beta(E) mutation was observed only on four haplotypes linked to framework 2. Type 2 haplotype was observed mainly from chromosomes of Tripura origin, but none from South Bengal. Homozygous E individuals with 1//1 genotype were significantly (P < 0.01) more anemic compared to individuals with 2//2 genotype. This work creates a database of hemoglobinopathy mutations for the population of Eastern India which will facilitate prenatal diagnosis and counseling. Am. J. Hum. Biol. 12:454-459, 2000. Copyright 2000 Wiley-Liss, Inc.