Genetic contribution to variation in atherothrombotic phenotypes in the Asian Indian population

2009 ◽  
Vol 102 (08) ◽  
pp. 379-388 ◽  
Author(s):  
Natesha Khadrinarasimhaih ◽  
Saikat Kanjilal ◽  
Manjari Mukerjee ◽  
Vijay Kakkar ◽  
Veena Rao

SummaryCoronary artery disease (CAD) is a multifactorial disease, and family history is the best available tool to assess gene-environment interaction. This study addressed the heritability of quantitative traits, namely lipid, coagulation/fibrinolysis and pro-inflammatory markers in the ongoing family-based Indian Atherosclerosis Research Study and assessed the effect of the type/lineage of CAD family history on inheritance patterns in the highrisk Indian population. A total of 518 families comprising 2,305 individuals were recruited in phase I of the IARS; of these, 1,195 individuals from 220 families were included in the heritability analysis. With the exception of leptin, all phenotypes exhibited significant age- and sex-adjusted heritability (p<0.0001). Amongst all the phenotypes analysed after adjustment for confounding factors, the significantly higher heritability estimates of triglycerides (0.53, p<0.0001), lipoprotein (a) (0.83, p<0.0001) and interleukin-6 (0.46, p<0.0001) with low spouse pair correlations identifies them as possible CAD risk factors. Families with parental history of CAD had onset of CAD symptoms at much younger ages with significantly higher heritability of proinflammatory markers, whereas in families with sibling history of CAD, more risk factors were present at significantly higher levels. Triglycerides, lipoprotein (a) and interleukin-6 appear to be promising atherothrombotic candidate phenotypes in this population. Genes controlling these phenotypes are possible candidate genes linked with CAD. An informed understanding and incorporation of ‘family history’ as a screening tool may help in the prevention and pre-emption of CAD.

Neurology ◽  
2017 ◽  
Vol 88 (17) ◽  
pp. 1642-1649 ◽  
Author(s):  
Frank J. Wolters ◽  
Sven J. van der Lee ◽  
Peter J. Koudstaal ◽  
Cornelia M. van Duijn ◽  
Albert Hofman ◽  
...  

Objective:To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort.Methods:From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI.Results:Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12–2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61–4.15; ≥80 years: HR 1.01, 95% CI 0.58–1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history.Conclusions:Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.


2012 ◽  
Vol 2 (1) ◽  
pp. 171-178 ◽  
Author(s):  
Anil Chankaramangalam Mathew ◽  
TG Prince ◽  
R Remees ◽  
N Saravanapandian ◽  
S Ramalingam ◽  
...  

Background In India, the prevalence of asthma has increased over the last two decades especially in children and young adults. The aim of the study was to estimate the prevalence of asthma in school going children aged 5-10 and 11-15 years in the city of Coimbatore and determine the risk factors associated with it. Materials and methods A school based cross-sectional study was conducted at the urban field practice area of PSGIMSR, Coimbatore between 1st June 2011 and 31st August 2011.  The questionnaire was filled by the parents and collected from the children. The data were analyzed using SPSS (11.5version). Results The prevalence of asthma among children aged 5-10 years was 9.5% (95%  Confidence Interval (CI) 7.49 – 11.50) and among children aged 11-15 years was 7.27% (95% CI 5.40 – 9.14). The Risk factors significantly associated with asthma among children aged 5-10 years were positive family history of asthma (Odds Ratio (OR)=3.10, 95% CI 1.80 - 5.36), longer duration of time spent in front of television and computer (OR=2.75, 95% CI 1.44 - 5.25), having food allergies (OR=2.36, 95% CI 1.19 - 4.68), and low birth weight of the child (OR=1.79, 95% CI 1.08 - 2.98). The factors significantly associated with asthma among children aged 11-15 years were positive family history of asthma (OR=2.99, 95% CI 1.34 - 6.64), poor ventilation (OR= 4.94, 95% CI 2.72 – 8.93), and use of pillows made up of wool, foam or synthetic material (OR=2.7, 95% CI 1.31 - 5.58). Conclusion Our data suggests that there is a high prevalence of asthma among school going children in Coimbatore. Parental history of asthma was a risk factor in both age groups studied. Television viewing for more than 2 hours, low birth weight and food allergy are additional risk factors for children aged 5-10 years. Poor ventilation and use of pillows made up of wool/ foam/ synthetic material are other risk factors in 11-15 years old children. Appropriate preventive strategies may help reduce the risk of asthma. Children with low birth weight and a family history of asthma need careful evaluation and long term follow up.DOI: http://dx.doi.org/10.3126/nje.v2i1.6378 Nepal Journal of Epidemiology 2012;2 (1):171-178 


1995 ◽  
Vol 41 (2) ◽  
pp. 241-245 ◽  
Author(s):  
S Bailleul ◽  
R Couderc ◽  
C Rossignol ◽  
J Fermanian ◽  
F Boutouchent ◽  
...  

Abstract The relation between lipoprotein(a) [Lp(a)], apolipoprotein (apo) E phenotypes, cholesterol, triglycerides, apo A-I, apo B, and a family history of atherosclerosis or risk factors was studied in 2- and 4-year-old French Caucasian children (n = 499). Lp(a) concentrations were distributed in a typical skewed manner and were found to be an independent lipid variable. The distribution of apo E phenotypes did not differ by gender. Cholesterol and apo B were under apo E phenotype control; Lp(a) was not. A significant positive relation was found between Lp(a) concentrations and the number of parental risk factors. Children whose grandparents had a history of cardiovascular disease had Lp(a) concentrations shifted towards higher values. Measurement of Lp(a) in children may help to identify those at an increased risk of atherosclerotic disease, especially when their parents have at least two relevant risk factors.


2020 ◽  
Vol 18 ◽  
Author(s):  
Akshaya Srikanth Bhagavathula ◽  
Abdullah Shehab ◽  
Anhar Ullah ◽  
Jamal Rahmani

Background: The increasing incidence of cardiovascular disease (CVD) threatens the Middle Eastern population. Several epidemiological studies have assessed CVD and its risk factors in terms of the primary prevention of CVD in the Middle East. Therefore, summarizing the information from these studies is essential. Aim: We conducted a systematic review to assess the prevalence of CVD and its major risk factors among Middle Eastern adults based on the literature published between January 1, 2012 and December 31, 2018 and carried out a meta-analysis. Methods: We searched electronic databases such as PubMed/Medline, ScienceDirect, Embase and Google Scholar to identify literature published from January 1, 2012 to December 31, 2018. All the original articles that investigated the prevalence of CVD and reported at least one of the following factors were included: hypertension, diabetes, dyslipidaemia, smoking and family history of CVD. To summarize CVD prevalence, we performed a random-effects meta-analysis. Results: A total of 41 potentially relevant articles were included, and 32 were included in the meta-analysis (n=191,979). The overall prevalence of CVD was 10.1% (95% confidence interval (CI): 7.1-14.3%, p<0.001) in the Middle East. A high prevalence of CVD risk factors, such as dyslipidaemia (43.3%; 95% CI: 21.5-68%), hypertension (26.2%; 95% CI: 19.6-34%) and diabetes (16%; 95% CI: 9.9-24.8%), was observed. The prevalence rates of other risk factors, such as smoking (12.4%; 95% CI: 7.7-19.4%) and family history of CVD (18.7%; 95% CI: 15.4-22.5%), were also high. Conclusion: The prevalence of CVD is high (10.1%) in the Middle East. The burden of dyslipidaemia (43.3%) in this region is twice as high as that of hypertension (26.2%) and diabetes mellitus (16%). Multifaceted interventions are urgently needed for the primary prevention of CVD in this region.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Inés Urrutia ◽  
◽  
Alicia Martín-Nieto ◽  
Rosa Martínez ◽  
J Oriol Casanovas-Marsal ◽  
...  

AbstractThe aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11–9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846–0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Florence Jaguga

Abstract Background Stuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors. Case presentation A 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms. Conclusion Clinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Malika A Swar ◽  
Marwan Bukhari

Abstract Background/Aims  Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck. Methods  This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. . Results  1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003&lt;0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075&lt;0.01-0.101-0.129,-0.072&lt;0.01BMI (mg/m2)0.0080.008,0.0101&lt;0.010.01130.019,0.013&lt;0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21 Conclusion  This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing. Disclosure  M.A. Swar: None. M. Bukhari: None.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1952
Author(s):  
Anna Johansson ◽  
Isabel Drake ◽  
Gunnar Engström ◽  
Stefan Acosta

Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56–0.68), high diet quality (HR = 0.83, 95% CI 0.72–0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80–0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.


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