Summary Background Elevated blood pressure and glucose, serum cholesterol, and body mass index (BMI) are risk factors for cardiovascular diseases (CVDs); some of these factors also increase the risk of chronic kidney disease (CKD) and diabetes. We estimated CVD, CKD, and diabetes mortality attributable to these four cardio-metabolic risk factors for all countries and regions between 1980 and 2010. Methods We used data on risk factor exposure by country, age group, and sex from pooled analysis of population-based health surveys. Relative risks for cause-specific mortality were obtained from pooling of large prospective studies. We calculated the population attributable fractions (PAF) for each risk factor alone, and for the combination of all risk factors, accounting for multi-causality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific PAFs by the number of disease-specific deaths from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all inputs to the final estimates. Findings In 2010, high blood pressure was the leading risk factor for dying from CVDs, CKD, and diabetes in every region, causing over 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths; and cholesterol for 10%. After accounting for multi-causality, 63% (10.8 million deaths; 95% confidence interval 10.1–11.5) of deaths from these diseases were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7.1 million deaths; 6.6–7.6) in 1980. The mortality burden of high BMI and glucose nearly doubled between 1980 and 2010. At the country level, age-standardised death rates attributable to these four risk factors surpassed 925 deaths per 100,000 among men in Belarus, Mongolia, and Kazakhstan, but were below 130 deaths per 100,000 for women and below 200 for men in some high-income countries like Japan, Singapore, South Korea, France, Spain, The Netherlands, Australia, and Canada. Interpretations The salient features of the cardio-metabolic epidemic at the beginning of the twenty-first century are the large role of high blood pressure and an increasing impact of obesity and diabetes. There has been a shift in the mortality burden from high-income to low- and middle-income countries.

OBJECTIVE-Recently, genome-wide association studies have provided evidence that several common variants within the fat mass-and obesity-associated (FTO) gene were significantly associated with obesity in populations of European origin. However, their effects in other ethnic populations remain to be elucidated. RESEARCH DESIGN AND METHODS-In this study, we examined the association between three FTO variants (rs8050136, rs9939609, and rs9930506) and obesity and related traits in a population-based study of 3,210 unrelated Chinese Han subjects from Shanghai and Beijing. In secondary analyses, we also tested for association with type 2 diabetes and related traits. Logistics regression and generalized linear models were used to test for additive and dominant effects of the risk alleles. RESULTS-The minor allele frequencies of rs8050136, rs9939609, and rs9930506 in our population (0.12, 0.12, and 0.20, respectively) were substantially lower than those observed for populations of European descent (e.g., for CEU population of HapMap: 0.45, 0.48, and 0.45, respectively). Despite our study being sufficiently powered to detect effects similar to those previously reported, none of the FTO SNPs were found to be associated with obesity, overweight, BMI, waist circumference, or body fat percentage. In addition, none of the SNPs exhibited significant associations with fasting levels of plasma glucose, A1C, insulin, or ␤-cell function (estimated via homeostasis model assessment) under either an additive or a dominant model in the quantitative trait analyses. Analyses stratified by sex or geographical region did not change these observations. O besity is a leading risk factor for multiple common diseases such as type 2 diabetes, heart disease, and hypertension and has a strong genetic component (1-4). However, identification of genetic determinants of obesity has proven to be difficult in the past decades despite numerous studies and extensive efforts. Recently, as part of a genome-wide association study for type 2 diabetes, Frayling et al. (5) identified a common variant, rs9939609, in the FTO gene that was strongly associated with BMI and obesity in 1,924 case and 2,939 control subjects from the U.K. This association was further replicated in 13 cohorts including 38,758 individuals of European descent, showing that each additional copy of the rs9939609 A-allele was associated with 0.36 kg/m 2 increase in BMI and increased the risk of being obese by 32% (5). Subsequently, several nearby single nucleotide polymorphisms (SNPs) (rs1421085, rs1781449, rs8050136, and rs9930506) were also found to be significantly associated with an increased risk of obesity in white European populations (6,7). However, these associations need to be confirmed by further replication studies, particularly in other ethnic populations. Furthermore, the differences in risk allele frequencies and linkage disequilibrium (LD) structure across ethnicities can provide further insights to refine the association signal and identify the true risk variant. Therefor...

Edited by Tamas DalmayKeywords: HOTAIR miR-193a c-KIT Acute myeloid leukemia a b s t r a c t HOTAIR is significantly overexpressed in various cancers and facilitates tumor invasion and metastasis. However, whether HOTAIR plays oncogenic roles in acute myeloid leukemia (AML) is still unknown. Here, we report that HOTAIR expression was obviously increased in leukemic cell lines and primary AML blasts. Clinically, AML patients with higher HOTAIR predicted worse clinical outcome compared with those with lower HOTAIR. Importantly, HOTAIR knockdown by small hairpin RNA inhibited cell growth, induced apoptosis, and decreased number of colony formation. Finally, HOTAIR modulated c-KIT expression by competitively binding miR-193a. Collectively, our data suggest that HOTAIR plays an important oncogenic role in AML and might serve as a marker for AML prognosis and a potential target for therapeutic intervention.

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