Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension.

BACKGROUND: The vitamin D receptor (VDR) gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS) influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition. AIM: The aim of this study was to evaluate association between VDRFok I polymorphism and genetic susceptibility to essential hypertension. MATERIALS AND METHODS: Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C) [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs) were calculated to predict the risk for developing hypertension by the individuals of different genotypes. RESULTS: The genotype distribution and allele frequencies of Fok I (T/C) [rs2228570] VDR polymorphism differed significantly between patients and controls (χ2 of 18.0; 2 degrees of freedom; P = 0.000). FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking. CONCLUSIONS: Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension.

High risk of essential hypertension in males with intron 4 VNTR polymorphism of eNOS gene.

In this study 250 patients with essential hypertension were investigated in comparison to 218 normotensives for association with epidemiological parameters. Of these DNA samples from 176 patients and 168 controls were analyzed for intron 4 27bp repeat polymorphism of eNOS gene. The study revealed significantly high risk of essential hypertension for individuals who were obese, with a positive family history and with non-vegetarian food habits. Though the intron 4b/a polymorphism of eNOS gene did not reveal any association with essential hypertension in general, males with a/a genotype of the polymorphism did show significantly high risk for developing hypertension.

Association of CYP1A1*2 polymorphisms with breast cancer risk: a case control study.

BACKGROUND: The Cytochrome P-4501A1 (CYP1A1) gene, located on chromosome 15q, is involved in the metabolism of carcinogens mainly polycyclic aromatic hydrocarbons as well as estrogen. It is considered as candidate gene for low-penetrance breast cancer susceptibility. Hence the present study aims to discuss the role of CYP1A1 polymorphisms in breast cancer. MATERIALS AND METHODS: A total of 250 breast cancer patients and the same number of healthy age-matched controls were analyzed for the polymorphism of CYP1A1*2 by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In the present study, association of CYP1A1*2 (Ile 462Val) polymorphism with breast cancer was studied. Only one breast cancer patient was observed to be homozygous for Val allele but none among controls. The frequency of heterozygous Ile/Val genotype was found to be increased significantly in breast cancer patients (68.1%) as compared to controls (51.0%). Higher frequency of heterozygotes for Val allele was observed among premenopausal breast cancer patients and patients with high BMI, positive for HER2/neu status and advanced stage of the disease in comparison to the corresponding groups. No significant association of CYP1A1*2 polymorphism was observed with occupation, estrogen receptor and progesterone receptor status of breast cancer patients. CONCLUSIONS: In conclusion, our results suggest a significant correlation between CYP1A1*2 expression and the occurrence of breast cancer.

Association of apolipoprotein E (RFLP) polymorphism with myopia.

BACKGROUND: Myopia or nearsightedness is a spherical error of refraction, whereby the images are focused in front of retina. Eye, being an organ rich in activated oxygen species, requires a high level of antioxidants to protect the unsaturated fatty acids. Apolipoprotein E (APOE) is one of the proteins that is produced by Muller cells within the retina and is also endowed with antioxidant properties. Genetic polymorphism of APO E is controlled by three common alleles e3, e2 and e4 and rare e1, e4v at the APOE structural gene locus. Different isoforms of APO E differ in their antioxidant properties, and the e4 allele has lesser ability to combat oxidative stress. AIMS: Myopia being a disease influenced by oxidative stress, the present study was undertaken to find association of myopia with APO E polymorphism. MATERIALS AND METHODS: A total of 187 myopic cases and 192 controls were genotyped for apolipoprotein E polymorphism. RESULTS: In both controls and myopic cases, E3/3 genotype was found to be the most frequent one. There was an increase in E3/4 genotype frequency among male probands, high myopia cases and probands with early age at onset, suggesting that the E3/4 genotype might confer risk for myopia development. CONCLUSION: This association with E3/4 genotype might predispose susceptible individuals to develop high myopia and early onset myopia.

Lipid profile and apolipoprotein E polymorphism in essential hypertension.

BACKGROUND: Studies in several populations have indicated that genetic variation at the apolipoprotein E structural locus influences atherosclerosis leading to cardiovascular diseases. The possible role of apolipoprotein E polymorphism in the development of essential hypertension has not been sufficiently investigated. In this case-control study, we aimed to determine the significance of association between essential hypertension and apolipoprotein E genotypes. In addition, apolipoprotein E genotypes were correlated with serum lipid levels in order to understand the possible interaction between the specific genotype and the lipid profiles that can contribute to hypertension. METHODS AND RESULTS: The apolipoprotein E genotypes were assayed in 185 patients and 200 controls by polymerase chain reaction followed by enzymatic digestion with Hha I. Using logistic regression analysis, the multivariate-adjusted odds of hypertension were calculated. The incidence of epsilon4 allele was found to be significantly higher in patients (12.16%) than in controls (5.75%, chi2=10.87; p<0.05) and also in patients with positive family history (16.7%) as compared to negative family history (8.87%, chi2 = 8.45; p<0.1). Further, it was observed that carriers of epsilon4 allele have twice as much risk (p<0.05) for developing hypertension as compared to carriers of other alleles. Patients with epsilon4 allele had significantly higher levels of total cholesterol and low-density lipoprotein- cholesterol as compared to epsilon4 allele non-carriers (p<0.05). The adjusted odds ratios for epsilon4 and epsilon2 alleles versus epsilon3 allele were 2.2 (95% confidence interval 1.2 to 3.8, p<0.05) and 1.2 (95% CI, 0.75 to 1.77, p<0.514), respectively. CONCLUSIONS: Our study revealed a strong association of apolipoprotein E locus with hypertension and lipid profile. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.

Study of families of nonsyndromic hearing impairment segregating with mutations in Cx26 gene.

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) is the most common form with profound hereditary hearing impairment linked to DFNB1 locus (connexin26 gene) at 13q12. Mutations in connexin26 (Cx26) gene are known to be frequently associated with ARNSHI. Here, we report results on 13 families with NSHI screened for entire coding region of Cx26 using ARMS-PCR, restriction digestion analysis, SSCP and sequencing. Cx26 mutations were found in seven of the 13 families with inheritance of W24X (G to A at 71bp) in six and R127H (G to A at 380bp) in one of them. The observations imply that the G to A transition at position 71 in exon2 of Cx26 gene could play a major role in the phenotypic expression of recessive hearing impairment while R127H could be an associated polymorphism in Indian population.

Plasma Lipoprotein (a) levels in patients with untreated essential hypertension.

Lipoprotein (a) [Lp (a)] is considered as a risk factor for vascular diseases, especially those associated with renal failure. Adequate studies have not been conducted on the lipoprotein (a) in essential hypertensive patients. There is a controversy on the mechanisms by which Lp (a) is associated with essential hypertension. It is unclear whether Lp (a) contributes to atherogenesis or to thrombogenesis or both. Recent studies suggest that Lp (a) can act as a marker for determining vascular or tissue injury. Reports on Indian population indicate elevated levels of Lp (a), together with other serum lipoproteins emphasizing an important role in Coronary Heart Disease (CHD) and peripheral atherosclerosis. In the present study we aimed to evaluate the relation between plasma levels of Lp (a) and the parameters of the lipid profile in a group of essential hypertensive patients, who are not receiving pharmacological treatment and with no clinical signs of associated pathologies or organ damage. A total of 37 essential hypertensive patients (27 men and 10 women) were compared with 50 controls (32 men and 18 women). It was observed that the hypertensive patients had higher plasma concentrations of Lp (a), Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), and Triglycerides (TG) as compared to controls (P< 0.01). Hypertensive patients were also observed to have significantly low levels of High-Density Lipoprotein Cholesterol levels (HDL-C) as compared to controls (P<0.01). Only 14 hypertension patients and 4 controls had plasma concentrations of Lp (a) of over 30 mg/dl. Lp (a) values correlated significantly ( P<0.05 ) with systolic blood pressure (SBP), diastolic blood pressure (DBP) and the main parameters of the lipid profile. We conclude that elevated plasma Lp (a) levels were associated with hypertension and show significant correlation with lipid levels. However higher plasma concentrations of Lp (a), albeit with in the normal range, could be an independent risk factor for atherosclerosis, and could contribute towards increasing the risk for cardiovascular disease in persons with essential hypertension.

Retinitis pigmentosum co-segregating with Enamel Hypoplasia (Amelogenesis Imperfecta)-A new Syndrome.

A family with the segregation of retinitis pigmentosum (RP) in combination with enamel hypoplasia (amelogenesis imperfecta - AI) is recorded. Family information collected over three generations revealed expression of the condition in two of the cousins born to half sibs. Parents of both the patients are cousins and are phenotypically normal. None of the sibs and other relatives of the patients are affected with any ophthalmic condition or dental anomalies. Ophthalmic evaluation of the patients revealed retinitis pigmentosa with nystagmus and optic atrophy and dental examination showed the presence of AI with hypoplastic enamel,' severe attrition of incisors and molars with narrowing of root canal and pulp chambers. Retinitis pigmentosum is a highly heterogeneous condition with 11 genes identified for an autosomal dominant, 13 for autosomal recessive and 5 for X-linked inheritance. Amelogenesis imperfecta is also a genetically heterogeneous condition showing all the three types of segregation. To the best of our knowledge co-segregation of RP with AI has not been reported. The family reported here may be considered as a new syndrome caused by a rare autosomal recessive gene with pleitropic effect affecting the retina and as well as the normal dentition. Alternatively it could also represent a rare coincidence of the two conditions.

Marfan Like Syndrome With Multiple Ocular Abnormalities.

An 18 year old female with multiple ocular disorders showed more or less cardinal features similar to that of an autosomal dominantly inherited Marfan Syndrome. Related features with variable symptoms were seen in her sibs. Major and minor manifestations of MFS like cardio-vascular, respiratory problems, spine deformities, arachnodactyly were not observed. Pedigree analysis showed high incidence of consanguinity.

Study of Idiopathic Generalized Epilepsy (IGE) cases for Segregation Analysis.

Epilepsy is a neurological disorder characterized by recurring seizures. A seizure is a paroxysmal and transitory disturbance of brain function that develops suddenly and terminates spontaneously. We studied 247 Idiopathic Generalised Epilepsy (IGE) cases referred to the Neurology Department of Nizam 's Institute of Medical Sciences, Hyderabad for genetic basis and also associations with certain genetic, biochemical and epidemiological factors to understand the mechanism of the onset and progression of the disease. Of the 247 cases studied 42.91% showed positive family history for IGE and also genetic heterogeneity with the possibility of segregation of the condition following autosomal dominant, recessive and sex linked inheritance. We made an attempt to estimate the segregation frequencies to determine the mode of inheritance in the families ascertained.

Evaluation Of LP (a) As A Risk Predictor For CAD In Angiorgaphiclly Tested Inividuals And Asymptomatic Controls.

Coronary Artery Disease (CAD) has reached epidemic proportions and has been attributed as the foremost cause of mortality worldwide. In the search for the causative factors, both genetic and non-genetic, Lipoprotein (a) has emerged as a powerful predictor for premature CAD. Lp(a) is a macromolecular complex found in human serum, strictly under genetic control, highly variable and resembling the low density lipoprotein cholesterol. In the present study, an attempt has been made to evaluate its predictive role by estimating its levels in patients with and without coronary artery disease (CAD) diagnosed by angiographic procedure. It was observed that Lp(a) levels increase with increasing severity of the disease albeit insignificantly. The observations made in the present study need to be substantiated by large scale studies.

Genetic Analysis Of Congenital Cataracts.

Congenital cataracts constitute a major cause of blindness in infancy. It is caused by the loss of transparency of the lens, hampering normal vision. Affected infants become visually handicapped necessitating effective management. Cataracts result when normal lens formation during embryogenesis and its subsequent development are affected. Based on the location and morphology of the opacities, different phenotypic forms of cataracts are identified which are under the control of different genes and follow autosomal dominant, autosomal recessive and X-linked inheritance. Crystallins (a, b and g) which constitute 90% of the water soluble proteins are responsible for the maintenance of the refractive property of the lens. Hence structural variations in these proteins have been associated with cataracts. Intrinsic membrane proteins which are water insoluble and expressed in the terminal differentiation of the lens epithelium are also implicated in cataract formation. Cataracts are found to be associated with maternal infections during pregnancy (rubella infection), several clinical syndromes, metabolic disorders, chromosomal disorders, (triploidy, trisomies, monosomy, deletions, duplications and translocations), and gene disorders. Autosomal dominant forms are found to be more common among the gene disorders and exhibit intrafamilial, interfamilial and interocular variations. More than a dozen genes have been mapped for cataracts showing the locus and allelic heterogeneity and two of them are associated with mutations in the crystallin genes. One of them with over expression of gE gene on chromosome 2 causes Coppock like cataract while a chain termination mutation in the crystallin BB2 locus on chromosome 22 causes Cerulean cataract. Experiments on animals suggest crystallins as strong candidates for the study of cataracts in man. Other candidate loci include intrinsic membrane proteins (MIP), developmental genes (PAX6) and connexin gap junction proteins (CX46). Surgical extraction of cataracts though is considered as the best treatment for cataracts, the prognosis is poor when it comes to infantile forms. Hence risk predictions and counseling based on the mode of inheritance and other factors seems to be the best approach in the management of cataracts. Recently prenatal detection of cataracts through ultrasonography has been reported which can be made a part of the routine anatomical study specially when family history for severe genetic disorder assoicated with cataracts exist.

Association Of GC Phenotypes With Pre-eclampsia-Possibility For A Causal Role.

Pre-eclampsia is a hypertensive disorder of pregnancy and has been reported to be associated with altered vitamin D levels. GC being a vitamin D binding protein, may be playing a functional role in the pathophysiology of the disease. The present investigation conducted on 100 pre-eclamptic and hypertensive controls with a corresponding decrease in GC 1-1 phenotype as compared to normotensive controls. There was no difference in the frequency of GC 2-2 phenotype between eclamptic women and controls. A similar trent was observed in moderate and severe cases of pre-eclampsia and in multigravid women with recurrence of pre-eclampsia. Relative risk estimates revealed an increased risk for moderate and severe types of pre-eclampsia when their phenotypes were of GC 2-1. The increase in heterozygote frequency of GC in pre-eclampsia and hypertensive controls as compared to normotensive controls, indicates the risk of GC 2-1 phenotype which could be due to a direct physiological effect against the disease through increased physiological versatility where the two alleles of GC may vary functionally. It may be possible that the binding capacity of GC alleles 1 and 2 with vitamin D may be varying on similar lines as haptoglobin with haemoglobin. The altered levels of vitamin D as reported by many authors and the increased risk of GC 2-1 phenotype observed in the present study indicate a possibility for a causal relationship of this phenotype with the disease probably With a functional role.

Multiple Regression Analysis Of Biochemical And Immunological Parameters In Essential Hypertension.

Data on 134 cases diagnosed for essential-hypertension (EHT) and studied for eight biochemical and five immunological parameters (blood sugar, blood urea, serum creatinine, serum cholesterol, serum protein, haptoglobin, Lactate dehydrogenase (LDH), ceruloplasmin, Ig-G, Ig-A, antinuclear antibody (ANA) T and B cell populations) along with 180 normotensive controls were computerised for their contributions by using the forward selection procedures of selecting the best regression equation (Draper and Smith, 1981). When biochemical parameters alone were considered, they contributed 10.0 per cent to the variation in diastolic blood pressure of which the contribution due to haptoglobin was 6.59 per cent and serum creatinine 3.41 per cent. When biochemical and immunological parameters were considered, only LDH contributed 15.30 per cent to the variation in diastolic blood pressure. When the data was grouped based on the expected diastolic pressure (mm/Hg;) into low risk (80-100) medium risk (101-110) and high risk (111-120) groups, males were found to be more prone in general. In the medium risk group 30.98per cent and high risk group 27.78per cent of the cases showed Positive family history while all the cases with low risk were non-familial. Among the familial cases compared to males, females were found to be 2.67 times higher in medium and 1.5 times higher in high risk groups suggesting greater involvement of genetic component in females and non-genetic and / or physiological factors in males.

A Sibship Of Bardet-Biedl Syndrome With Hepatocellular Damage.

A sibship of two, a brother and sister with the cardinal features of recessively inherited Bardet-Biedel syndrome (BBS) with three other affected relatives is described. All the affected, expect one in the family of six generations were born to consanguineous parents. Clinical feature in the probands included cardinal features of BBS along with strikingly short metacarpals. Biochemical estimations on the two affected sibs revealed elevated liver enzymes, prolonged clotting and prothrombin time, suggesting liver cell damage or dysfunction. This is a first report of such an association of hepatocellular damage with BBS.

ABO Blood Group Antibodies and ABH Secretion In Duodenal Ulcers.

The association of the ABO antigen-antibody titres with the ABH secretor status in duodenal ulcers was examined in a sample of 196 patients and 182 healthy controls. The risk for group A and group B patients depended upon the strengths of the antigens and the ABH secretor status. Further the risk was high for low antibody titres in non-secretor patients than in secretor patients. Increased demand on the antibodies for mucoprotection in the absence of the A and B antigens in the gastro-intestinal mucosa or insufficient production of antibody by the lymphocytes could be the possible reasons.