Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
Ontology highlight
ABSTRACT:
SUBMITTER: Natarajan P
PROVIDER: S-EPMC8042019 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
Natarajan Pradeep P Pampana Akhil A Graham Sarah E SE Ruotsalainen Sanni E SE Perry James A JA de Vries Paul S PS Broome Jai G JG Pirruccello James P JP Honigberg Michael C MC Aragam Krishna K Wolford Brooke B Brody Jennifer A JA Antonacci-Fulton Lucinda L Arden Moscati M Aslibekyan Stella S Assimes Themistocles L TL Ballantyne Christie M CM Bielak Lawrence F LF Bis Joshua C JC Cade Brian E BE Do Ron R Doddapaneni Harsha H Emery Leslie S LS Hung Yi-Jen YJ Irvin Marguerite R MR Khan Alyna T AT Lange Leslie L Lee Jiwon J Lemaitre Rozenn N RN Martin Lisa W LW Metcalf Ginger G Montasser May E ME Moon Jee-Young JY Muzny Donna D O'Connell Jeffrey R JR Palmer Nicholette D ND Peralta Juan M JM Peyser Patricia A PA Stilp Adrienne M AM Tsai Michael M Wang Fei Fei FF Weeks Daniel E DE Yanek Lisa R LR Wilson James G JG Abecasis Goncalo G Arnett Donna K DK Becker Lewis C LC Blangero John J Boerwinkle Eric E Bowden Donald W DW Chang Yi-Cheng YC Chen Yii-Der I YI Choi Won Jung WJ Correa Adolfo A Curran Joanne E JE Daly Mark J MJ Dutcher Susan K SK Ellinor Patrick T PT Fornage Myriam M Freedman Barry I BI Gabriel Stacey S Germer Soren S Gibbs Richard A RA He Jiang J Hveem Kristian K Jarvik Gail P GP Kaplan Robert C RC Kardia Sharon L R SLR Kenny Eimear E Kim Ryan W RW Kooperberg Charles C Laurie Cathy C CC Lee Seonwook S Lloyd-Jones Don M DM Loos Ruth J F RJF Lubitz Steven A SA Mathias Rasika A RA Martinez Karine A Viaud KAV McGarvey Stephen T ST Mitchell Braxton D BD Nickerson Deborah A DA North Kari E KE Palotie Aarno A Park Cheol Joo CJ Psaty Bruce M BM Rao D C DC Redline Susan S Reiner Alexander P AP Seo Daekwan D Seo Jeong-Sun JS Smith Albert V AV Tracy Russell P RP Vasan Ramachandran S RS Kathiresan Sekar S Cupples L Adrienne LA Rotter Jerome I JI Morrison Alanna C AC Rich Stephen S SS Ripatti Samuli S Willer Cristen C Peloso Gina M GM
Nature communications 20210412 1
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholester ...[more]
Similar Datasets
Project description:This study was undertaken to ascertain the effect of an aqueous suspension of a commonly available preparation of edible clay ("takere") on serum lipid profiles and atherogenic indices of normal Wistar rats. Ninety-five adult Wistar rats of average weight of 100 g were assigned into seven groups. Group 1 (Baseline) was immediately sacrificed at the commencement of study; Group 2 (Control) daily received distilled water, orally; and Groups 3 to 7 received via the same route (per body weight), 125 mg/kg (T125), 250 mg/kg (T250), 500 mg/kg (T500), 1,000 mg/kg (T1000), and 2,000 mg/kg (T2000) of the takere suspension, respectively, for 28 days. In week 1, the treatments significantly (p < 0.05) lowered the levels of serum triglyceride (by T250, T1000, and T2000), VLDL cholesterol (by T250, T1000, and T2000), and atherogenic index of plasma (AIP; by T250) and significantly (p < 0.05) raised the levels of serum HDL (T250), LDL (T250 and T2000), non-HDL (T2000) cholesterols, atherogenic coefficient (AC; T2000), cardiac risk ratio (CRR; T2000), and Castelli's risk index II (CRI-II; T2000) of the rats. In week 2, the treatments significantly (p < 0.05) lowered the levels of serum triglyceride (T2000), HDL (T125, T500, T1000, and T2000), VLDL (T2000) cholesterols and significantly (p < 0.05) raised levels of serum LDL (T125, T1000, and T2000), non-HDL (T125, T1000, and T2000) cholesterols, AC (T125, T500, and T1000), CRR (T125, T500, and T1000), CRI-II (T125 and T1000), AIP (T125, T500, and T1000) of the rats. In week 4, the treatments significantly (p < 0.05) raised the levels of serum total (T500 and T2000), HDL (T2000), non-HDL (T500 and T1000) cholesterols, AC (T500), CRR (T500), and CRI-II (T500). This result indicates that the consumption of takere suspension may have adverse effects on serum lipid profiles and atherogenic indices of Wistar rats, at least at the doses administered in this study.
| S-EPMC6418444 | biostudies-other
Project description:BackgroundThe role of metabolic states in cardiovascular risks among individuals with varying degrees of obesity is unknown. The study aimed to compare cardiometabolic index (CMI), atherogenic index of plasma (AIP), lipid accumulation product (LAP) and novel anthropometric indices in metabolic and non-metabolically obese individual with regard to the role of FTO gene in Iranian adults.MethodsIn total, 165 individuals were recruited into this cross-sectional study. Individuals grouped into four groups: metabolic healthy normal-weight (MHNW) individuals, metabolically unhealthy normal-weight (MUNW) individuals, metabolically healthy obese (MHO) individuals and metabolic unhealthy obese (MUO) individuals. The dietary intake was evaluated by food frequency questionnaire (FFQ). The cardiovascular indices (CMI, AIP and LAP) were calculated. A variety of anthropometric indices were calculated, including body adiposity Index (BAI), weight-adjusted-waist index (WWI), A body shape index (ABSI) and waist-height ratio (WHR). The genotypes of FTO-rs9939609 subjects were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe individuals with metabolically unhealthy phenotypes (MUO, MUNW) have higher levels of triglyceride and cardiovascular indices (AIP, LAP and CMI) than the individuals with metabolic healthy phenotypes (MHO, MHNW). With a similar degree of obesity, the anthropometric indices (BAI, WWI and WHR) levels were higher in metabolic unhealthy groups than metabolically healthy groups. The highest frequency of obesity-risk allele AA of FTO gene was observed in MUO, MHO, MUNW and MHNW, respectively.ConclusionNormal-weight individuals with metabolic unhealthy status are at higher risk for cardiovascular diseases than obese individuals with metabolically healthy status. The genotype frequencies of obesity-risk allele AA of FTO gene were higher in obesity phenotypes than metabolic phenotypes.
| S-EPMC7322142 | biostudies-literature
Project description:BackgroundAnnexin A6 (AnxA6) is a lipid-binding protein that regulates cholesterol homeostasis and secretory pathways. However, the correlation of AnxA6 polymorphism with lipometabolism has never been studied in psoriasis.ObjectivesTo investigate the impact of AnxA6 polymorphism on lipid profiles and the expression of AnxA6 protein in both peripheral blood mononuclear cells (PBMCs) and lipometabolism in psoriasis.MethodsA total of 265 psoriatic patients received methotrexate (MTX) treatment for 12 weeks, after which their lipid profiles were determined by measuring total cholesterol (TC), triglycerides (TGs), lipoprotein (a) [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein (a)1 (ApoA1), and apolipoprotein B (ApoB). In addition, AnxA6 (rs11960458) was genotyped in 262 patients and the expression of AnxA6 in PBMCs was measured by Western blotting at baseline and week 8 post-MTX treatment.ResultsThe CC genotype carriers of rs11960458 had a lower expression of AnxA6 and lower levels of the pro-atherogenic lipids TC, LDL, and ApoB compared to TC genotype carriers. MTX significantly downregulated the levels of the anti-atherogenic lipids HDL-C and ApoA1 and the level of AnxA6 in TC genotype carriers, as well as the level of TGs in CC genotype carriers.ConclusionsThe polymorphism of AnxA6, rs11960458, was statistically associated with the levels of pro-atherogenic lipids and with the downregulation of MTX on the levels of anti-atherogenic lipids and TGs in psoriasis.
| S-EPMC9737844 | biostudies-literature
Project description:Brain-derived neurotrophic factor (BDNF) belongs to the "neurotrophin" family of growth factors, and it has recently been associated to cardiovascular disease (CVD). We anticipated that BDNF Val66Met polymorphisms may alter CVD risk markers such as serum lipid profile differences, and interaction with total antioxidant capacity of diet (DTAC) could alter these clinical parameters. This cross-sectional study consisted of 667 diabetic patients (39.7% male and 60.3% female). DTAC was calculated by international databases. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α). interleukin 18 (IL18), leptin and ghrelin were measured by standard protocol. Atherogenic indices (AIP, AC, CR-I, CR-II) were calculated. Genotyping of the BDNF Val66Met polymorphisms was conducted by the real-time PCR-RFLP method. The gene-diet interactions were evaluated using a generalized linear mode (GLMs). Carriers of the Val/Met genotype who were in the higher median intake of FRAP had lower HDL (P:0.04) and higher TG (P:0.005), AIP (P:0.02) and AC (P:0.02) index compared to Val/Val genotypes with lower median intake. Moreover, diabetic patients with Val/Met genotype who consumed higher ORAC intake had increased odds for anthropometric indices (BMI (P:0.01) and WC (P:0.03)), lipid profiles (TG) (P:0.01), and atherogenic index (AIP) (P:0.02), also decreased odds for HDL (P:0.03) concentration compared to reference group whit lower ORAC intake. Individuals with Val/Met genotype who consumed higher TRAP intake had increased odds for WC (P:0.04), TC (P:0.001), TG (P < 0.001), AIP (P < 0.001) and AC (P < 0.001). Finally, Val/Met patients with a higher median intake of TEAC had higher TG (P:0.02), AIP (P:0.009) and AC (P:0.03) compared to the reference group whit lower TEAC intake. Our study showed that Val/Met genotype had also the highest lipid profile and atherogenic indices even in the highest adherence to DTAC. While it seems that the presence of the Val/Val wild-type and BDNF Met/Met homozygotes in diabetic patients with a high DTAC is a protective factor.
| S-EPMC8476521 | biostudies-literature
Project description:BackgroundAdverse childhood experiences (ACE) have been associated with poor later life health outcomes, including cardiovascular disease (CVD). Limited research investigating potential underlying biological mechanisms linking ACE to CVD exists, particularly regarding lipid biomarkers.ObjectivesThe aim of this study was to examine the associations between childhood adversity and unfavourable lipid profiles and derived atherogenic risk indices in a middle-to-older aged population.MethodsThis cross-sectional study includes 1820 participants from the Mitchelstown cohort (49% male) in Ireland. Participants' self-reported history of childhood adversity (overall and by subtypes household dysfunction, abuse and neglect) were assessed through a validated 10-item ACE questionnaire. Lipid profiles were determined and atherogenic risk indices including Castelli's Risk Index 1 and 2 (CRI-I and CRI-II), Atherogenic Coefficient (AC) and Atherogenic Index Plasma (AIP) were generated. Logistic regression analysed ACE associations with unfavourable lipid outcomes, controlling for potential confounders.ResultsACE history (reported by 23% of sample), in particular childhood exposure to household dysfunction, was associated with later-life non-optimal TG and HDL-C concentrations and atherogenic risk indices CRI-II and AC in age and sex-adjusted models (all p < 0.05). In fully adjusted models, adults reporting ACE or exposure to household dysfunction were approximately twice as likely to have pro-atherogenic CRI-II relative to adults with no ACE (OR = 1.86, 95% CI: 1.19-2.92, p = 0.006 and OR = 2.19, 95% CI: 1.33-3.61, p = 0.002, respectively). Sex-stratified analysis demonstrated sex-specific associations.ConclusionsThis study provides evidence that ACEs are common among older adults in Ireland and are associated with unfavourable lipid profiles and derived atherogenic risk indices.
| S-EPMC10119964 | biostudies-literature
Project description:Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations.Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/μL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) μg/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations.Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes.
| S-EPMC4718242 | biostudies-literature
Project description:BackgroundSeveral previous studies have reported that dyslipidemia is associated with the risk of hypertension, but these studies are mainly conducted in European and US populations, with a very few studies in the Asian population. Moreover, the effects of atherosclerotic indices, including atherogenic coefficient (AC) and atherogenic risk of plasma (AIP), on hypertension in Asians have not been well described so far.MethodsFrom 2010 to 2016, altogether 211,833 Chinese adults were ultimately recruited at the health centers in 11 Chinese cities (including Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, and Nantong). Differences in continuous variables between the two groups were analyzed by the Mann-Whitney test, while those in categorical variables were examined by the Chi-squared test. Logistic regression was applied to evaluate the association between lipid profiles and the risk of hypertension. The predictive values of AC and AIP for the incidence of hypertension were analyzed using the area under the receiver operating characteristic (ROC) curve. Meanwhile, Bayesian network (BN) models were performed to further analyze the associations between the different covariates and the incidence of hypertension.ResultsA total of 117,056 participants were included in the final analysis. There were significant differences in baseline characteristics between normotension and hypertension groups (p < 0.001). In multivariate logistic regression, the risk of hypertension increased by 0.2% (1.002 [1.001-1.003]), 0.2% (1.002 [1.001-1.003]), and 0.2% (1.002 [1.001-1.003]) per 1 mg/dl increase in total cholesterol (TC), low-density lipoprotein (LDL), and non-high-density lipoprotein cholesterol (non-HDL-c), respectively. However, after adjusting for body mass index (BMI), an increase in HDL level was associated with a higher risk of hypertension (p for a trend < 0.001), and the risk of hypertension increased by 0.6% per 1 mg/dl increase in HDL-c (1.006 [1.003-1.008]). In women, AC had the highest predictive value for the incidence of hypertension with an area under the curve (AUC) of 0.667 [95% confidence interval (CI): 0.659-0.674]. BN models suggested that TC and LDL were more closely related to the incidence of hypertension.ConclusionsOverall, lipid profiles were significantly abnormal in the hypertensive population than in the normotensive population. TC and LDL were strongly associated with the incidence of hypertension. TC, LDL, and non-HDL-c levels show a positive association, HDL-c shows a negative association, while TG is not significantly associated with the risk of hypertension. After adjusting for BMI, HDL-c turns out to be positively associated with the risk of hypertension. In addition, AC has a good predictive value for the incidence of hypertension in women.
| S-EPMC9152277 | biostudies-literature
Project description:Sarcopenia is an age-related muscle senescence disease that leads to functional limitations, physical disability and premature death in older adults. Atherogenic index of plasma (AIP) is a novel indicator of atherosclerotic status based on triglycerides and high-density lipoprotein cholesterol. The aim of this study was to investigate the association between AIP and new-onset sarcopenia and its components among middle-aged and older adults in a Chinese community. This cohort study included 7,992 participants who were free of sarcopenia in 2011 in the China Health and Retirement Longitudinal Study and were followed up in 2013 and 2015. Sarcopenia was assessed using the recommendations of the Asian Working Group for Sarcopenia 2019. Longitudinal associations between AIP and sarcopenia and its components were assessed using Cox proportional risk regression modeling. The results showed that AIP was negatively associated with sarcopenia [HR and 95% CI: 0.73 (0.62-0.86)]; with muscle mass [β and 95%CI: 0.49 (0.4-0.57)], skeletal muscle mass index [β and 95%CI: 0.17 (0.15-0.2)], and grip strength [β and 95% CI: 0.17 (0.15-0.2)] being positively correlated. A lower AIP was associated with a lower muscle mass and handgrip strength and higher incidence of sarcopenia. Regular measurement of AIP in the middle-aged and older population in the community can help in the early diagnosis and intervention of sarcopenia.
| S-EPMC11742044 | biostudies-literature
Project description:BackgroundLipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature.ObjectiveTo determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals.MethodsThis cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05.ResultsLAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables.ConclusionLAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.
| S-EPMC5941956 | biostudies-other
Project description:ContextWe hypothesized that, similar to the coordinated homeostatic regulation of most hormones, the concentration of free and bioavailable 25-hydroxyvitamin D [25(OH)D] will be tightly controlled by total 25(OH)D and vitamin D binding protein (VDBP) and that the VDBP concentrations will be associated with insulin resistance status.ObjectiveOur primary objective was to investigate associations between total, free, and bioavailable 25(OH)D and VDBP. We also evaluated the relationships of VDBP with insulin resistance indices.Study designThe study design was cross-sectional in the setting of a university children's hospital. The relative concentration of bioavailable 25(OH)D to total 25(OH)D [bioavailable 25(OH)D/total 25(OH)D was expressed as a percentage [percentage bioavailable 25(OH)D].ResultsSubjects were 47, postmenarchal, female adolescents, with a mean age of 15.8±1.4 years, a mean body mass index of 23.1±4.0 kg/m2. The total 25(OH)D was strongly associated with VDBP (rho=0.57, P<.0001). At lower total 25(OH)D concentrations, the concentration of bioavailable 25(OH)D relative to total 25(OH)D was higher (23.8% vs 14.9%, P<.0001), whereas the relative concentration of free 25(OH)D was similar (P=.44). VDBP was inversely associated with fasting insulin (rho=-0.51, P=.0003) and homeostatic model assessment of basal insulin resistance (rho=-0.45, P=.002) and positively with whole-body insulin sensitivity (rho=0.33, P=.02); these relationships persisted after adjusting for percentage fat and attenuated after adjusting for race.ConclusionOur data suggest that VDBP concentrations are regulated by total 25(OH)D levels to maintain adequate concentrations of bioavailable 25(OH)D. VDBP concentrations are inversely associated with hyperinsulinemia and insulin resistance.
| S-EPMC3879668 | biostudies-literature