Search PubMed⌕ Search

Biomedical subjects

Shah Ebrahim

Publications and source records attributed to Shah Ebrahim.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE.

Identification of unknown mutations has remained laborious, expensive, and only viable for studies of selected cases. Population-based "reference ranges" of rarer sequence diversity are not available. However, the research and diagnostic interpretation of sequence variants depends on such information. Additionally, this is the only way to determine prevalence of severe, moderate, and silent mutations and is also relevant to the development of screening programs. We previously described a system, meltMADGE, suitable for mutation scanning at the population level. Here we describe its application to a population-based study of MC4R (melanocortin 4 receptor) mutations, which are associated with obesity. We developed nine assays representing MC4R and examined a population sample of 1,100 subjects. Two "paucimorphisms" were identified (c.307G>A/p.Val103Ile in 27 subjects and c.-178A>C in 22 subjects). Neither exhibited any anthropometric effects, whereas there would have been >90% power to detect a body mass index (BMI) effect of 0.5 kg/m(2) at P=0.01. Two "private" variants were also identified. c.335C>T/p.Thr112Met has been previously described and appears to be silent. A novel variant, c.260C>A/p.Ala87Asp, was observed in a subject with a BMI of 31.5 kg/m(2) (i.e., clinically obese) but not on direct assay of a further 3,525 subjects. This mutation was predicted to be deleterious and analysis using a cyclic AMP (cAMP) responsive luciferase reporter assay showed substantial loss of function of the mutant receptor. This population-based mutation scan of MC4R suggests that there is no severe MC4R mutation with high prevalence in the United Kingdom, but that obesity-causing MC4R mutation at 1 in 1,100 might represent one of the commonest autosomal dominant disorders in man.

Aged↗
PubMed2007

The association of the paraoxonase (PON1) Q192R polymorphism with depression in older women: findings from the British Women's Heart and Health Study.

BACKGROUND: The association between the R allele of PON1 Q192R and symptoms reported by sheep dippers and Gulf War veterans has been used to suggest a biological basis for these symptoms. In the absence of such studies in non-occupational populations, these conclusions may not be valid. OBJECTIVE: To examine the association of paraoxonase (PON1) Q192R with a report of ever being diagnosed with depression among a random sample of 3266 British women, aged 60-79 years. RESULTS: The R allele of PON1 Q192R was associated with depression: per-allele odds ratio 1.22 (95% confidence interval: 1.05 to 1.41) in this population. CONCLUSIONS: These findings suggest that the association of PON1 Q192R with symptoms of depression in occupationally exposed groups may be driven by exposure to toxins that everyone in the general population is exposed to rather than exposure to toxins specifically used by sheep dippers or Gulf War veterans, or that other mechanisms underlie the association. This is because the study population in which we have found an association consisted of British women aged 60-79 years, few of whom were sheep dippers or Gulf War veterans. When using genotype-outcome associations to infer causality with respect to an environmental exposure modified by the genotype, it is important to examine these associations in general populations and in those specifically exposed to the putative agent. The possible role of PON1 Q192R in psychiatric morbidity requires further examination.

Aged↗
PubMed2006

Socio-economic position and the use of preventive health care in older British women: a cross-sectional study using data from the British Women's Heart and Health Study cohort.

BACKGROUND: Socio-economic inequalities in health may be due to differential uptake of preventive and therapeutic medical services. OBJECTIVES: To examine socio-economic position and self-reported use of six preventive services in a cohort of older British women. METHODS: Women randomly selected from general practice age/sex registers in 23 towns were examined from 1998 to 2001. Of all, 3652 women aged 62-83 years completed a questionnaire in 2003 assessing preventive service use. RESULTS: Women from manual social classes were less likely to have recent flu vaccinations [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.74, 0.98] and dental (OR 0.42, 95% CI 0.36, 0.49), eye (OR 0.77, 95% CI 0.67, 0.88) or chiropody examinations (OR 0.88, 95% CI 0.77, 1.01). Manual social class was not related to having recent blood pressure or cholesterol checks. CONCLUSIONS: Among older British women, preventive services for cardiovascular disease are not socially patterned. However, those from lower socio-economic groups are less likely to have recent flu vaccinations and dental, eye and chiropody examinations.

Aged↗
PubMed2006

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Adult↗
PubMed2006

Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study.

OBJECTIVE: To investigate risk factors, such as heavy alcohol consumption, that might explain any increased risk of haemorrhagic stroke associated with low blood cholesterol. DESIGN: Prospective cohort study. SETTING: Korea. PARTICIPANTS: 787,442 civil servants (661,700 men, 125,742 women) aged 30-64. MAIN OUTCOME MEASURES: Cardiovascular risk factors were assessed at biennial health check. Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems. RESULTS: 6328 cases of ischaemic stroke (6021 men, 307 women), 3947 cases of haemorrhagic stroke (3748 men, 199 women), 3170 cases of undefined stroke (2902 men, 268 women), and 4417 cases of myocardial infarction (4305 men, 112 women) occurred. Ischaemic stroke and myocardial infarction were strongly and positively associated with blood cholesterol (hazard ratio per 1 mmol/l cholesterol 1.20 (95% confidence 1.16 to 1.24) and 1.48 (1.43 to 1.53), respectively). Haemorrhagic stroke showed an inverse association in fully adjusted models (0.91, 0.87 to 0.95). This inverse association was confined to participants with hypertension. When stratified by concentration of gamma glutamyl transferase (GGT), an indicator of alcohol consumption, the association was not seen in participants with low concentrations of GGT, and it was independent of hypertension in those with high concentrations of GGT (> 80 U/l).

Adult↗
PubMed2006

Integrated single-label liquid-phase assay of APOE codons 112 and 158 and a lipoprotein study in British women.

BACKGROUND: Apolipoprotein E (APOE) is an important element of lipid metabolism and, hence, cardiovascular disorders. APOE has 3 main allelic variants: epsilon3, epsilon4, and epsilon2. Of these, epsilon3 is the most common, followed by epsilon4 and epsilon2. The associations of these isoforms with cardiovascular disorders and Alzheimer disease have been widely studied in different populations. Most of the genotyping in these studies has been performed with gel-based methods, which have important limitations, particularly for large epidemiologic studies. We therefore developed an integrated "one-tube" liquid-phase assay. METHODS: To measure APOE isoforms, we developed an integrated single-label liquid-phase fluorescence assay containing 2 PCR primers, 2 probes, and 2 quencher oligonucleotides. We used a 384-well LightTyper, but the assay would be generically applicable for use with any fluorescence detector with thermal ramp control. We validated this method and applied it in the British Women's Heart and Health Study. RESULTS: There were 4 melting peaks, at 41, 56, 61, and 69 degrees C, which generated 6 distinctive patterns representing genotypic combinations of epsilon3, epsilon4, and epsilon2. The magnitude and direction of the associations found with total cholesterol, HDL-cholesterol, triglycerides, and estimated LDL-cholesterol were consistent with previous reports. CONCLUSION: The one-tube LightTyper assay presented here enables accurate, convenient, and economical genotyping of APOE and can be used for large epidemiologic studies.

Aged↗
PubMed2006

Self-reported smoking cessation interventions were not associated with quitting in older women.

OBJECTIVE: To determine the extent to which smoking cessation interventions are used in the community and their relative success in older women. STUDY DESIGN AND SETTING: Prospective cohort study located in 23 general practices in England, Scotland. and Wales and including 3,622 women aged 60 to 79 years at recruitment from the British Women's Heart and Health Study. RESULTS: Of the 370 smokers at baseline, 77 (21%) had stopped smoking at 3 years, reducing the prevalence of smoking from 10.2% to 8.8%. Women who were light smokers (<10 per day) at baseline were more likely to have quit than heavier smokers. The most common interventions reported by women who smoked at baseline were advice from a general practitioner (GP), family or friend's advice, and use of nicotine replacement, but 42% of the women reported having no intervention to help them to stop smoking. None of the individual interventions were associated with increased odds of quitting smoking over the follow-up period. Women reported finding a GP's advice, referral to a clinic, and nicotine replacement more useful than complementary treatments (acupuncture and hypnotherapy) or advice from family and friends. CONCLUSION: Smoking cessation rates in this study were in line with national targets and surveys. Self-reports of ever receiving interventions were not associated with quitting smoking among these older women. Different and innovative approaches to smoking cessation may need to be developed, and evaluated in future randomized clinical trials, for individuals who have smoked for a long period of time and for whom other smoking cessation interventions have not proved successful.

Age Distribution↗
PubMed2006

The association of oestrogen receptor alpha-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study.

AIMS: One previous study among women with established coronary heart disease found a gene-treatment interaction between the oestrogen receptor gene (ESR1) and hormone replacement in their association with high density lipoprotein cholesterol (HDL-c). We aimed to replicate these findings in a general population sample. METHODS AND RESULTS: Cross-sectional associations were assessed in a study of 3404 women from 23 towns across Britain who were aged 60-79 at the time of assessment and were described as white by the examining nurse. Women with the T-A haplotype [constructed from two single nucleotide polymorphisms (SNPs) in the first intron of ESR1: c454-397T > C (rs2234693) and c454-351A > G (rs9340799)], which was predicted to be associated with reduced oestrogen response, were more likely to have been past [per haplotype odds ratio 1.16 (95% CI 1.01, 1.33), P = 0.02] or to be current users [per haplotype odds ratio 1.19 (95% CI 0.99, 1.42), P = 0.05] of hormone replacement. However, there was no association between haplotype or either SNP and HDL-c or other cardiovascular disease risk factors and no statistical evidence of an interaction between hormone replacement use and haplotype or either SNP with respect to HDL-c or any other cardiovascular disease risk factors. CONCLUSION: Women with the T-A haplotype are more likely to use hormone replacement. However, genotyping of ESR1 rs2234693 or rs9340799 in post-menopausal women to tailor hormone replacement is unlikely to markedly improve cardiovascular risk.

Aged↗
PubMed2006

Informal care at times of change in health and mobility: a qualitative study.

INTRODUCTION: Relationships between people with health problems and their partners, families and friends are usually described as 'informal care'. Using a qualitative examination of older people's descriptions of their relationships with partners or other significant friends or relatives at times of change in health and mobility (walking), we questioned whether 'informal care' is an appropriate label. METHODS: Seven men and eight women aged between 58 and 85 years (mean 72.4 years) were recruited on grounds of having difficulty walking. Participants were interviewed on four occasions each. Nine of the interviewees lived with partners, four of whom were also interviewed. Whether living alone or with a partner, all participants discussed key social relationships. Analysis was performed using standard methods of qualitative inquiry, including thematic and narrative case study approaches. FINDINGS: The participants had several ways of coping with health changes and the onset or escalation of immobility. These included working together to ensure recovery, working together to maintain independence and experiencing and recognising considerable difficulty coping with change. Adaptation within relationships reflected the experience of abrupt or gradual change as well as expectations for the future. Participants did not describe their relationships in terms of 'carer' and 'cared for'. CONCLUSION: Means of coping with changing circumstances in mobility and health are inextricable from the work that goes on within partner, familial or friendship relationships. As older people seldom describe their relationships with significant others as 'care', it may be more appropriate to discuss informal care provision with patients by using the language of relationships.

Aged↗
PubMed2006

Sib-recruitment for studying migration and its impact on obesity and diabetes.

BACKGROUND: Urban-rural comparisons are of limited relevance in examining the effects of urban migration in developing countries where urbanisation is due to growth of existing urban populations, expansion of urban boundaries, and rural in-migration. Cultural, genetic and life-style backgrounds of migrants and host populations further limit the value of rural-urban comparisons. Therefore we evaluated a sib-comparison design intended to overcome the limitations of urban-rural comparisons. METHODS: Using the framework of a current cardiovascular risk factor screening study conducted in Indian factories, we recruited the non-migrant rural sibs of migrant urban factory workers and the urban sibs of non-migrant factory workers. The response rate, completed interviews and examinations conducted were assessed. Adequacy of generic food frequency questionnaires and WHO quality of life questionnaire were assessed. RESULTS: All the urban factory workers and spouses approached agreed to be interviewed. Of the 697 participants interviewed, 293 (42%) had at least one rural dwelling sibling. Twenty (22%) siblings lived further than 100 km from the study site. An additional 21 urban siblings of non-migrant factory workers were also investigated to test the logistics of this element of the study. Obesity (BMI >25 kg/m2) was more common in rural sibs than urban factory workers (age adjusted prevalence: 21.1% (17.1 to 25.0) vs. 16.1% (11.9, 20.3). Diabetes prevalence (fasting plasma glucose greater than 126 mg/dl) was higher than expected (age-adjusted prevalence: 12.5% (22 out of 93) in urban migrants and 4.5% (8 out of 90) in rural non-migrant sibs. CONCLUSION: The sib-comparison design is robust and has been adopted in the main study. It is possible that simple urban-rural study designs under-estimate the true differences in diabetes risk between migrants and non-migrants.

Journal Article↗
PubMed2006

Adult blood pressure and climate conditions in infancy: a test of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

The authors hypothesized that individuals born in the early 20th century who experienced the hottest and driest summers during infancy would be more likely to have suffered severe infant diarrhea and dehydration, and consequently have had higher blood pressure in adulthood, than those who experienced cooler and wetter summers. In this context, these climate data act as an instrumental variable for the association of early-life dehydration with later blood pressure. For 3,964 randomly selected British women born between 1919 and 1940 and whose blood pressure was measured at age 60-79 years, a one standard deviation (1.3 degrees C) higher mean summer temperature in the first year of life was associated with a 1.12-mmHg (95% confidence interval: 0.33, 1.91) higher adult systolic blood pressure, and a one standard deviation higher mean summer rainfall (33.9 mm) was associated with lower systolic blood pressure (-1.65 mmHg, 95% confidence interval: -2.44, -0.85). Equivalent results for diastolic blood pressure were 0.11 (95% confidence interval: -0.65, 0.86) and -0.32 (95% confidence interval: -0.71, 0.05). The climate variables were not associated with potential confounding factors such as socioeconomic position or lifestyle risk factors. These findings provide some evidence in favor of the hypothesis that dehydration in infancy is associated with higher adult blood pressure.

Aged↗
PubMed2006

Secondary prevention of coronary heart disease in older patients after the national service framework: population based study.

OBJECTIVE: To examine the extent of uptake of medication for secondary prevention of coronary heart disease in older British men and women before (1998-2001) and after (2003) the implementation of the national service framework. DESIGN: Two population based, longitudinal studies of men and women aged 60-79 in 1998-2001, based in one general practice in each of 24 British towns. PARTICIPANTS: Men and women with established coronary heart disease at the two time points (respectively 817 and 465 in 1998-2001, 857 and 548 in 2003), aged 60-79 in 1998-2001. MAIN OUTCOME MEASURES: Prevalence of use of antiplatelet medication, statins, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and other blood pressure lowering treatments (individually and in combination) assessed in 1998-2001 and 2003. RESULTS: Between 1998-2001 and 2003, the use of all individual drugs had increased in both men and women, especially for statins (from 34% to 65% in men and from 48% to 67% in women with myocardial infarction). However, less than half received beta blockers and ACE inhibitors, even by 2003. Prevalences of medication use were lower in patients with angina than in those with myocardial infarction. The proportions of patients receiving more than one drug increased over time; by 2003 about half of patients with myocardial infarction and a third of those with angina were receiving antiplatelet medication, statins, and blood pressure lowering treatments. CONCLUSIONS: Between 1998-2001 and 2003, statin uptake and the use of combined drug treatment in elderly men and women increased markedly. Further potential exists, however, for reducing the risk of recurrent coronary heart disease in older patients, particularly by improving the uptake of medication among angina patients, and by more extensive use of blood pressure lowering treatment (particularly with beta blockers and ACE inhibitors).

Adrenergic beta-Antagonists↗
PubMed2006

Psychological distress, loneliness and disability in old age.

With the growth in the number of older people, an increase of mental health problems might be expected. Reducing the amount of suffering and dependence due to poor mental health in old age is a priority requiring a good understanding of the determinants of psychological distress. The objectives were: (a) to measure the prevalence of psychological distress and loneliness in old men and women, living in the community, (b) to clarify the association between psychological distress, health and other explanatory variables and (c) to determine relationship between loneliness and psychological distress. We performed a cross-sectional study of 999 people aged 65+. The variables studied were psychological distress (GHQ-12) and self-reported loneliness. The prevalence of psychological distress was 20%. Illness and disability are related to psychological distress in old age; the feeling of loneliness is the single most important predictor of psychological distress, and not knowing neighbours increases the probability of depression. Attempts to improve detection and management of psychological distress in sick older people, in those who appear isolated and express loneliness should be evaluated.

Age Factors↗
PubMed2006

Association of body mass index measured in childhood, adolescence, and young adulthood with risk of ischemic heart disease and stroke: findings from 3 historical cohort studies.

BACKGROUND: It is unclear whether early life body mass index (BMI; in kg/m(2)) is associated with adult cardiovascular disease. OBJECTIVE: The objective was to assess the association of early life BMI with the risk of ischemic heart disease (IHD) and stroke. DESIGN: The association between early life BMI and risk of adult mortality from IHD and stroke was assessed in 3 historical cohort studies in which height and weight had been assessed by using standard procedures. Participants were traced and linked to national mortality data. Participants in the 3 cohorts were born between 1922 and 1937, 1927 and 1956, and 1928 and 1950 and were aged 2-15, 9-18, and 16-22 y, respectively, at the time of assessment of their height and weight. RESULTS: Participants in all 3 cohorts had mean BMIs similar to those reported for contemporary children and young adults, but fewer of the cohort participants were overweight or obese. BMI was not associated with future risk of IHD or stroke in any cohort. The pooled (all 3 cohorts) adjusted hazard ratio per SD of early life BMI was 1.09 (95% CI: 1.01, 1.19) for IHD and 0.94 (95% CI: 0.82, 1.08) for stroke. The pooled hazard ratio of IHD when participants who were overweight or obese for their age were compared with all other participants was 1.34 (95% CI: 0.95, 1.91), and no association was found between overweight or obesity and stroke risk. The effects of BMI did not vary by cohort or by age. CONCLUSION: These results do not provide strong evidence that being overweight or obese in childhood is associated with future cardiovascular disease risk.

Adolescent↗
PubMed2006

The association of the PON1 Q192R polymorphism with complications and outcomes of pregnancy: findings from the British Women's Heart and Health cohort study.

It has been hypothesised that paraoxonase genes would be related to adverse pregnancy outcomes, via a maternal or fetal effect on placental hypoperfusion and thrombosis. To date only two studies have assessed this possibility. In this study we assessed the associations of the PON1 Q192R polymorphism with self-report of having pregnancy-induced hypertension, gestational hyperglycaemia and a preterm offspring birth. The associations were assessed in 3266 white women who were randomly selected from 23 British towns. There was no association between PON1 Q192R and either self-report of pregnancy-induced hypertension or gestational hyperglycaemia but the prevalence of reporting having a preterm birth increased with each R allele: per allele odds ratio 1.20 [95% confidence interval (CI) 1.03, 1.41]. When our results were pooled with the one previous study of the association of this polymorphism with preterm birth, the pooled per allele odds ratio was 1.19 [95% CI 1.02, 1.39]. Our findings provide some further evidence to suggest that PON1 Q192R is associated with preterm birth; they invite further investigation of both maternal and fetal genotype for PON1 Q192R in relation to preterm birth.

Aged↗