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Blood multiomics reveal insights into population clusters with low prevalence of diabetes, dyslipidemia and hypertension.

ABSTRACT: Diabetes, dyslipidemia and hypertension are important metabolic diseases that impose a great burden on many populations worldwide. However, certain population strata have reduced prevalence for all three diseases, but the underlying mechanisms are poorly understood. We sought to identify the phenotypic, genomic and metabolomic characteristics of the low-prevalence population to gain insights into possible innate non-susceptibility against metabolic diseases. We performed k-means cluster analysis of 16,792 subjects using anthropometric and clinical biochemistry data collected by the Taiwan Biobank. Nuclear magnetic resonance spectra-based metabolome analysis was carried out for 217 subjects with normal body mass index, good exercise habits and healthy lifestyles. We found that the gene APOA5 was significantly associated with reduced prevalence of disease, and lesser associations included the genes HIF1A, LIMA1, LPL, MLXIPL, and TRPC4. Blood plasma of subjects belonging to the low disease prevalence cluster exhibited lowered levels of the GlycA inflammation marker, very low-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, valine and leucine compared to controls. Literature mining revealed that these genes and metabolites are biochemically linked, with the linkage between lipoprotein metabolism and inflammation being particularly prominent. The combination of phenomic, genomic and metabolomic analysis may also be applied towards the study of metabolic disease prevalence in other populations.

SUBMITTER: Su MW

PROVIDER: S-EPMC7058291 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Blood multiomics reveal insights into population clusters with low prevalence of diabetes, dyslipidemia and hypertension.

Su Ming-Wei MW Chang Chung-Ke CK Lin Chien-Wei CW Ling Shiu-Jie SJ Hsiung Chia-Ni CN Chu Hou-Wei HW Wu Pei-Ei PE Shen Chen-Yang CY

PloS one 20200305 3

Diabetes, dyslipidemia and hypertension are important metabolic diseases that impose a great burden on many populations worldwide. However, certain population strata have reduced prevalence for all three diseases, but the underlying mechanisms are poorly understood. We sought to identify the phenotypic, genomic and metabolomic characteristics of the low-prevalence population to gain insights into possible innate non-susceptibility against metabolic diseases. We performed k-means cluster analysis ...[more]

PMID: 32134946

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Project description:BackgroundHypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.MethodsWe conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.ResultsTotaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10-9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10-8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10-8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10-9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10-8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10-8]).ConclusionsThis study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

Project description:BackgroundCardiovascular disease is the most prevalent cause of morbidity and mortality in diabetic patients. Hypertension (HTN) has been confirmed as a major risk factor for cardiovascular disease, which is frequently associated with diabetes mellitus (DM). Therefore, the detection and management of elevated blood pressure (BP) is a critical component of the comprehensive clinical management of diabetics. Since the rates of hypertension in diabetics are lacking in Afghanistan, this study aimed to evaluate the prevalence of elevated blood pressure in type-2 diabetic patients.Materials and methodsThis is a descriptive cross-sectional study, which included 321 type -2 diabetic patients (119 males, 202 females) with a mean age of 53.86 ± 11.54 years who were presented to the Noble OPD center from November 2019 to January 2020.ResultsThe elevated blood pressure was detected in 70.5% of the patients. It was more prevalent in women than men (76.8% and 59.7% respectively). The mean systolic blood pressure was 146.94 ± 23.19 mmHg and mean diastolic blood pressure was 89.61 ± 11.59 mmHg. The mean pulse pressure was 57.32 ± 15.58 mmHg and the mean arterial pressure was 48.98 ± 7.73 mmHg. The mean body weight was 73.09 ± 13.75 Kg. The mean duration of diabetes mellitus was 7.08 ± 5.95 years with the average HbA1c of 9.27 ± 2.41%. The mean body mass index (BMI) of the patients was noted 28.77 ± 5.58 kg/m2.ConclusionThis study showed high prevalence of hypertension in type-2 diabetes patients with a significant difference in the rate of elevated blood pressure between males and females (it was higher in females than males). The systolic blood pressure had a positive correlation with age. However, it was insignificant for diastolic blood pressure. Healthcare providers and other health sector should work in collaboration for designing appropriate preventive strategies targeting the modifiable risk factors associated with hypertension.

Project description:BackgroundCardiovascular diseases are among the most common causes of hospital admissions and deaths in Zanzibar. This study assessed prevalence of, and antecedent factors and care access for the two common cardiovascular risk factors, hypertension and diabetes, to support health system improvements.MethodsData was from a population based nationally representative survey. Prevalence of hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or a self-reported diagnosis of hypertension; diabetes was defined as a fasting blood glucose ≥6.1 mmol/L or a self-reported diagnosis of diabetes. Care-cascades for hypertension and diabetes were created with four stages: being tested, diagnosed, treated, and achieving control. Multivariable logistic regression models were constructed to evaluate individual-level factors - including symptoms of mental illness - associated with having hypertension or diabetes, and with progressing through the hypertension care cascade. Whether people at overt increased risk of hypertension or diabetes (defined as > 50 years old, BMI > 30 kg/m2, or currently smoking) were more likely to be tested was assessed using chi squared.ResultsPrevalence of hypertension was 33.5% (CI 30.6-36.5). Older age (OR 7.7, CI 4.93-12.02), some education (OR 0.6, CI 0.44-0.89), obesity (OR 3.1, CI 2.12-4.44), and raised fasting blood glucose (OR 2.4, CI 2.38) were significantly independently associated with hypertension. Only 10.9% (CI 8.6-13.8) of the entire hypertensive population achieved blood pressure control, associated factors were being female (OR 4.8, CI 2.33-9.88), formally employed (OR 3.0, CI 1.26-7.17), and overweight (OR 2.5, CI 1.29-4.76). The prevalence of diabetes was 4.4% (CI 3.4-5.5), and associated with old age (OR 14.1, CI 6.05-32.65) and almost significantly with obesity (OR 2.1, CI 1.00-4.37). Only 11.9% (CI 6.6-20.6) of the diabetic population had achieved control. Individuals at overt increased risk were more likely to have been tested for hypertension (chi2 19.4) or diabetes (chi2 33.2) compared to the rest of the population. Symptoms of mental illness were not associated with prevalence of disease or progress through the cascade.ConclusionHigh prevalence of hypertension and suboptimal management along the care cascades indicates a large unmet need for hypertension and diabetes care in Zanzibar.

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Blood multiomics reveal insights into population clusters with low prevalence of diabetes, dyslipidemia and hypertension.

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Blood multiomics reveal insights into population clusters with low prevalence of diabetes, dyslipidemia and hypertension.

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