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author:("sooner, J. S.")
1.  Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians 
Diabetologia  2011;55(4):981-995.
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
All studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC3296006  PMID: 22109280
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
2.  Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis 
Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs.
Materials and methods
A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry.
Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects.
The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.
PMCID: PMC1869046  PMID: 17181565
Atherosclerosis; coronary calcification; endothelial progenitor cells; ethnicity; intima-media thickness
3.  Homocysteine: a novel risk factor for coronary heart disease in UK Indian Asians 
Heart  2001;86(2):121-122.
PMCID: PMC1729859  PMID: 11454816
4.  Cost effectiveness of ramipril treatment for cardiovascular risk reduction 
Heart  2001;85(5):539-543.
OBJECTIVE—To assess the cost effectiveness of ramipril treatment in patients at low, medium, and high risk of cardiovascular death.
DESIGN—Population based cost effectiveness analysis from the perspective of the health care provider in the UK. Effectiveness was modelled using data from the HOPE (heart outcome prevention evaluation) trial. The life table method was used to predict mortality in a medium risk cohort, as in the HOPE trial (2.44% annual mortality), and in low and high risk groups (1% and 4.5% annual mortality, respectively).
SETTING—UK population using 1998 government actuary department data.
MAIN OUTCOME MEASURE—Cost per life year gained at five years and lifetime treatment with ramipril.
RESULTS—Cost effectiveness was £36 600, £13 600, and £4000 per life year gained at five years and £5300, £1900, and £100 per life year gained at 20 years (lifetime treatment) in low, medium, and high risk groups, respectively. Cost effectiveness at 20 years remained well below that of haemodialysis (£25 000 per life year gained) over a range of potential drug costs and savings. Treatment of the HOPE population would cost the UK National Health Service (NHS) an additional £360 million but would prevent 12 000 deaths per annum.
CONCLUSIONS—Ramipril is cost effective treatment for cardiovascular risk reduction in patients at medium, high, and low pretreatment risk, with a cost effectiveness comparable with the use of statins. Implementation of ramipril treatment in a medium risk population would result in a major reduction in cardiovascular deaths but would increase annual NHS spending by £360 million.

Keywords: angiotensin converting enzyme inhibitor; cardiovascular risk; cost effectiveness; ramipril
PMCID: PMC1729730  PMID: 11303006
5.  Abnormalities of vascular endothelial function may contribute to increased coronary heart disease risk in UK Indian Asians 
Heart  1999;81(5):501-504.
OBJECTIVE—To test the hypothesis that abnormalities of endothelial function are present in Indian Asians and may contribute to their increased coronary heart disease risk.
SETTING—Single centre in west London.
PATIENTS—26 Indian Asian and 18 European white healthy male subjects, aged 35 to 61 years recruited from general practice lists.
DESIGN—Brachial artery diameter responses to reactive hyperaemia and sublingual glyceryl trinitrate were compared using high resolution ultrasound.
RESULTS—Mean (SEM) flow mediated, endothelium dependent dilatation was reduced in Indian Asians compared with European whites, at 3.2 (0.8)% v 5.9 (1.0)%, p = 0.03. In contrast, there were no significant differences in baseline brachial arterial diameter (4.6 (0.1) v 4.6 (0.1) mm, p = 0.65) or glyceryl trinitrate induced dilatation (18.8 (1.5)% v 18.5 (1.7)%, p = 0.90) between Indian Asians and European whites, respectively. Univariate analysis showed that Indian Asian race was significantly associated with impaired flow mediated dilatation (regression coefficient = −2.8 (1.3)%, p = 0.03), and in multivariate analysis, this relation was independent of both conventional coronary heart disease risk factors and markers of insulin resistance.
CONCLUSIONS—Endothelial function is impaired in healthy UK Indian Asians compared with European whites, and the defect is not accounted for by major coronary heart disease risk factors. Endothelial function may be modulated by novel risk factors in Indian Asians.

Keywords: endothelial function; Indian Asians; coronary heart disease; risk factors
PMCID: PMC1729047  PMID: 10212168
8.  Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography. 
Journal of Clinical Investigation  1996;98(9):2094-2099.
Patients with coronary artery disease or heart failure have been shown to be insulin resistant. Whether in these patients heart muscle participates in the insulin resistance, and whether reduced blood flow is a mechanism for such resistance is not known. We measured heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia (insulin clamp) in 15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities. Six age- and weight-matched healthy subjects served as controls. Regional glucose uptake was measured by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose (FDG), blood flow was measured by the H2(15)O method. Myocardial glucose utilization was measured in regions with normal perfusion and wall motion as assessed by radionuclide ventriculography. Whole-body glucose uptake was 37+/-4 micromol x min(-1) x kg(-1) in controls and 14+/-2 mciromol x min(-1) x kg(-1) in patients (P = 0.001). Myocardial blood flow (1.09+/-0.06 vs. 0.97+/-0.04 ml x min(-1) x g(-1), controls vs. patients) and skeletal muscle (arm) blood flow (0.046+/-0.012 vs. 0.043+/-0.006 ml x min(-1) x g(-1)) were similar in the two groups (P = NS for both). In contrast, in patients both myocardial (0.38+/-0.03 vs. 0.70+/-0.03 micromol x min(-1) x g(-1), P = 0.0005) and muscle glucose uptake (0.026+/-0.004 vs. 0.056+/-0.006 micromol x min(-1) x g(-1), P = 0.005) were markedly reduced in comparison with controls. In the whole dataset, a direct relationship existed between insulin-stimulated glucose uptake in heart and skeletal muscle. Patients with a history of myocardial infarction and a low ejection fraction are insulin resistant. This insulin resistance affects both the myocardium and skeletal muscle and is independent of blood flow.
PMCID: PMC507654  PMID: 8903329

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