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1.
Artigo em Inglês | MEDLINE | ID: mdl-31669095

RESUMO

BACKGROUND: Clinical and epidemiological studies have shown that obesity is associated with asthma and that these associations differ by asthma subtypes. Little is known about the shared genetic components between obesity and asthma. OBJECTIVE: To identify shared genetic associations between obesity-related traits and asthma subtypes in adults. METHODS: A cross-trait genome-wide association study (GWAS) was performed using 457,822 individuals of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma via GWAS was sought using results from obese vs. lean mouse RNA-seq and RT-PCR experiments. RESULTS: We found a substantial positive genetic correlation between BMI and later-onset asthma defined by asthma age of onset at 16 years of age or older (Rg =0.25, P=9.56×10-22). Mendelian Randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and GTEx tissue eQTLs, shared immune- and cell differentiation-related pathways between obesity and asthma. Finally, RNA-seq data from lungs of obese versus control mice found that two genes (ACOXL and MYL6) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by RT-PCR in an independent set of mice. CONCLUSIONS: Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma, and identifying molecular pathways that may underlie both obesity and asthma.

2.
Curr Opin Clin Nutr Metab Care ; 22(6): 465-471, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31577641

RESUMO

PURPOSE OF REVIEW: The current review is to summarize the recent progress in the research of the relation between vitamin D and bone mineral density (BMD) during weight-loss interventions, and describe how genetic factors interact with weight-loss interventions on changes in bone health. RECENT FINDINGS: Obesity has shown to be a protective factor for bone health, whereas the relation between weight loss and BMD has yet to be well established. Although beneficial on a variety of metabolic outcomes, weight-loss interventions, such as dietary modifications and surgical treatment, showed adverse effects on bone health in some studies. Despite the biological plausibility for a role of vitamin D in promoting bone health, current evidence does not consistently support the connection between changes in circulating vitamin D levels and BMD during weight loss, partly because of insufficient vitamin D levels during weight loss. Genome-wide association studies have identified genetic variants related to the blood levels of vitamin D; and emerging evidence suggests that dietary intakes may modify the relationship between genetically determined circulating vitamin D levels and change in BMD in response to weight-loss diets. SUMMARY: The relations of changes in circulating vitamin D levels with bone health during weight-loss interventions remain to be established, and the role of genetic factors would be considered in future investigations.

3.
JAMA Netw Open ; 2(10): e1913131, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31603489

RESUMO

Importance: The American Heart Association (AHA) introduced the Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health. However, several shortcomings of these metrics have been identified. Therefore, a revised set of LS7 metrics was developed. Objectives: To evaluate national trends in the metrics addressed by the revised LS7 and the individual and combined associations of the revised LS7 metrics with all-cause and cause-specific mortality and to compare these measures with the AHA recommended LS7 metrics. Design, Setting, and Participants: This national cross-sectional study used data from the National Health and Nutrition Examination Survey from 1988 to 2016. The revised LS7 metrics included a combination of the body mass index and waist to hip ratio, Healthy Eating Index-2010, and a lower blood pressure threshold of greater than or equal to 130/80 mm Hg in addition to physical activity, smoking, total cholesterol, and fasting blood glucose. Data for this study were analyzed from June 1, 2017, to December 31, 2017. Main Outcomes and Measures: The primary outcome was all-cause mortality. The secondary outcome was cancer and cardiovascular disease (CVD) mortality. Results: Data were available for 13 606 adults in 1988 to 1994 (7329 [53%] female; mean [SD] age, 47 [17.7] years), 6360 in 1999 to 2004 (3442 [54%] female; mean [SD] age, 47 [18.6] years), 10 618 in 2005 to 2010 (5428 [51%] female; mean [SD] age, 47 [17.5] years), and 10 773 in 2011 to 2016 (5474 [50%] female; mean [SD] age, 48 [17.4] years). Compared with a revised LS7 score of 0 to 1, the adjusted hazard ratios for a revised LS7 score of 5 to 7 were 0.46 (95% CI, 0.35-0.61) for all-cause mortality, 0.42 (95% CI, 0.25-0.68) for cancer mortality, and 0.37 (95% CI, 0.24-0.55) for CVD mortality, respectively. The adjusted hazard ratios for participants who met 6 or more AHA recommended ideal LS7 metrics were 0.49 (95% CI, 0.33-0.74) for all-cause mortality, 0.60 (95% CI, 0.29-1.25) for cancer mortality, and 0.24 (95% CI, 0.13-0.47) for CVD mortality. Participants with a body mass index of 29.9 or less but without central obesity were independently associated with lower risk of all-cause and CVD mortality. Blood pressure was associated with 36.7% or more of the observed population-attributable fraction of mortality. Conclusions and Relevance: The individual revised LS7 metrics with modified criteria regarding weight, blood pressure, and diet provide more information about factors associated with cancer mortality than the original AHA LS7 metrics.

4.
J Am Heart Assoc ; 8(20): e012556, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31576770

RESUMO

Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods and Results A total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self-reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow-up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84-0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74-0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84-1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity. Conclusions In urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

5.
Environ Res ; 179(Pt A): 108775, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31593837

RESUMO

BACKGROUND: Recent studies suggested an inverse association between exposures to perfluoroalkyl substances (PFASs) and bone mineral density (BMD). Whether exposures to PFASs are also associated with changes in BMD has not been examined. METHODS: Five major PFASs (perfluorooctanesulfonic acid, PFOS; perfluorooctanoic acid, PFOA; perfluorohexanesulfonic acid, PFHxS; perfluorononanoic acid, PFNA; perfluorodecanoic acid, PFDA) and BMD (g/cm2) at six bone sites (spine, total hip, femoral neck, hip intertrochanteric area, hip trochanter, and hip Ward's triangle area) were measured at baseline among 294 participants in the POUNDS-LOST study, a weight-loss trial, of whom a total of 175 participants had BMD measured at both baseline and year 2. Linear regression was used to model the differences or changes in BMD for each SD increment of PFAS concentrations. In a secondary analysis, interactions between PFASs and baseline body mass index (BMI), as well as a BMI-related genetic risk score (GRS) derived from 97 BMI-predicting SNPs were examined in relation to changes in BMD. RESULTS: At baseline, both PFOS and PFOA were significantly associated with lower BMD at several sites. For each SD increase of PFOS, the ßs (95% CIs) for BMD were -0.020(-0.037, -0.003) for spine, -0.013(-0.026, 0.001) for total hip, -0.014(-0.028, 0.000) for femoral neck, and -0.013(-0.026, 0.000) for hip trochanter. For PFOA, the corresponding figures were -0.021(-0.038, -0.004) for spine, -0.015(-0.029, -0.001) for total hip, and -0.015(-0.029, -0.002) for femoral neck. After adjusting for baseline covariates and 2-year weight change, higher baseline plasma concentrations of PFOS, PFNA, and PFDA were associated with greater reduction in BMD in the hip; the ßs (95% CIs) were -0.005(-0.009, -0.001), -0.006(-0.010, -0.001), and -0.005(-0.009, -0.001), respectively. Similar associations were found in hip intertrochanteric area for all PFASs except PFHxS, with ßs ranging from -0.006 for PFOA to -0.008 for PFOS and PFNA. Participants with a higher GRS tended to have less PFAS-related BMD decline in total hip (Pinteraction = 0.005) and the hip intertrochanteric area (Pinteraction = 0.021). There were similar PFAS-related BMD changes by baseline BMI levels, although the interactions did not achieve statistical significance. CONCLUSIONS: This study demonstrated that higher plasma PFAS concentrations were not only associated with a lower BMD at baseline, but also a faster BMD loss in a weight-loss trial setting. Genetic predisposition to larger body size may somewhat attenuate the deleterious effects of PFASs on BMD. Further exploration of the possible impact of PFAS exposures on bone density is warranted.

6.
Hypertension ; : HYPERTENSIONAHA11913510, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31656094

RESUMO

High blood pressure (BP) is closely related to obesity, and weight loss lowers BP. Evidence has shown considerable interpersonal variation of changes in BP among people experiencing weight loss, and such variation might be partly determined by genetic factors. We assessed the changes in systolic and diastolic BP (SBP/DBP) among 692 participants randomly assigned to 1 of 4 diets varying in macronutrient content for 2 years. Two separate polygenic scores (SBP/DBP-PGS derived from 52/50 single nucleotide polymorphisms) were built for each participant based on 66 BP-associated single nucleotide polymorphisms. During a 2-year intervention, participants in the bottom versus upper tertile of SBP/DBP-PGS had a greater decrease in SBP (△SBP at 6, 12, and 24 months: -3.84 versus -1.61, -4.76 versus -2.75, -2.49 versus -1.63; P=0.001) or in DBP (△DBP at 6, 12, and 24 months: -3.09 versus -1.34, -2.69 versus -1.44, -1.82 versus -0.53; P<0.001). We also found gene-diet interaction on changes in SBP from baseline to 24 months (Pinteraction=0.009). Among participants assigned to a high-protein diet, those with a lower SBP-polygenic scores had greater decreases in SBP at months 6 (P=0.018), months 12 (P=0.007), and months 24 (P=0.089); while no significant difference was observed across the SBP-polygenic scores tertile groups among those assigned to an average-protein diet (all P values >0.05). Our data indicate that genetic susceptibility may affect BP changes in response to weight-loss diet interventions, and protein intake may modify the genetic associations with changes in BP. This trial was registered at URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.

8.
World J Surg Oncol ; 17(1): 152, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472673

RESUMO

BACKGROUND: In some malignant tumors, a high neutrophil-to-lymphocyte ratio (NLR) is connected with unfavorable prognosis. Nevertheless, the prognostic value of the NLR in gliomas remains disputed. The clinical significance of the NLR in gliomas was investigated in our study. METHODS: The databases, PubMed, Embase, and the Cochrane Library, were searched using words like "glioma," "glioblastoma," "neutrophil-to-lymphocyte ratio," and others through May 2019. We evaluated the significance of NLR on overall survival (OS) of patients with gliomas in our study. RESULTS: Finally, 16 cohorts with 2275 patients were analyzed. The pooled analysis revealed that an elevated NLR was connected with unfavorable OS (hazards ratio (HR): 1.43, 95% confidence interval (CI): 1.27-1.62) outcomes of patients with gliomas. CONCLUSION: A high NLR can be considered a high-risk prognostic factor in gliomas, and more adjuvant chemotherapy should be recommended for high-risk patients.

9.
Clin Nutr ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542245

RESUMO

AIMS: Women with prior gestational diabetes mellitus (GDM) or high genetic susceptibility are prone to development of type 2 diabetes. We examined whether a lifestyle intervention modified the genetic effect on changes in glycemic markers among women with prior GDM. RESEARCH DESIGN AND METHODS: This study included 560 women with prior GDM from a randomized controlled trial, the Tianjin Gestational Diabetes Mellitus Prevention Program, who were assigned into an intervention arm (improved physical activity and healthy dietary intakes) or a control arm. We assessed associations of GDM related genetic variants in/near the CDKAL1 (rs7754840) and MTNR1B (rs10830962) genes with changes in fasting levels of glucose and insulin, ß-cell function (HOMA-B) and insulin resistance (HOMA-IR) at 1 year and 2 years after the baseline. RESULTS: We found significant interactions between CDKAL1 variant rs7754840 and lifestyle intervention on changes in fasting insulin and HOMA-IR at 1 year (P for interactions = 0.008 and 0.006, respectively). The GDM-increasing C allele was associated with a 0.07-unit greater increase in fasting insulin (P = 0.048) and HOMA-IR (P = 0.045) in the control group, while opposite-directional associations were observed in the intervention group; women with the C allele seemed to decrease more in these glycemic markers than the non-C-carriers (both P ≤ 0.06). The interactions between the CDKAL1 genetic variant and lifestyle intervention on changes in fasting insulin (P = 0.035) and HOMA-IR (P = 0.024) remained significant over the 2-year period, even though the effects of lifestyle intervention were attenuated at 2-year. The MTNR1B variant rs10830962 did not show interaction with lifestyle intervention on changes in the glycemic markers. CONCLUSIONS: Healthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01554358. URL OF REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01554358.

10.
BMJ Open ; 9(7): e022877, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31371282

RESUMO

OBJECTIVE: We tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI). DESIGN: Three FADS variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies. SETTING: Population based study. PARTICIPANTS: 11 323 women from the Nurses' Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women's Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS). MAIN OUTCOMES: Long-term (~10 years) changes in BMI and body weight. RESULTS: In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the FADS rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the FADS rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the FADS rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2 per g, p=3×10-5) than the rs174570 non-T carriers (beta=0.16 kg/m2 per g, p=0.08). Similar results were observed for fish intake. CONCLUSIONS: Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the FADS variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.

11.
Diabetes Care ; 42(8): 1365-1371, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31332027

RESUMO

OBJECTIVE: Type 2 diabetes is related to obesity and altered bone health, and both are affected by gut microbiota. We examined associations of weight loss diet-induced changes in a gut microbiota-related metabolite trimethylamine N-oxide (TMAO), and its precursors (choline and l-carnitine), with changes in bone mineral density (BMD) considering diabetes-related factors. RESEARCH DESIGN AND METHODS: In the 2-year Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost), 264 overweight and obese participants with measurement of BMD by DXA scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intake. Association analysis was performed in pooled participants and different diet groups. Changes in blood levels of TMAO, choline, and l-carnitine from baseline to 6 months after the dietary intervention were calculated. RESULTS: We found that a greater reduction in plasma levels of TMAO from baseline to 6 months was associated with a greater loss in whole-body BMD at 6 months and 2 years (P = 0.03 and P = 0.02). The greater reduction in TMAO was also associated with a greater loss in spine BMD (P = 0.005) at 2 years, independent of body weight changes. The associations were not modified by baseline diabetes status and glycemic levels. Changes in l-carnitine, a precursor of TMAO, showed interactions with dietary fat intake in regard to changes of spine BMD and hip BMD at 6 months (all P < 0.05). Participants with the smallest decrease in l-carnitine showed less bone loss in the low-fat diet group than the high-fat diet group (P spine = 0.03 and P hip = 0.02). CONCLUSIONS: TMAO might protect against BMD reduction during weight loss, independent of diet interventions varying in macronutrient content and baseline diabetes risk factors. Dietary fat may modify the relation between change in plasma l-carnitine level and changes in BMD. Our findings highlight the importance of investigating the relation between TMAO and bone health in patients with diabetes.

12.
Am J Clin Nutr ; 110(3): 759-768, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301130

RESUMO

BACKGROUND: Whether changes in fruit and vegetable intake can modify the effect of genetic susceptibility to obesity on long-term changes in BMI and body weight are uncertain. OBJECTIVE: We analyzed the interactions of changes in total and specific fruit and vegetable intake with genetic susceptibility to obesity in relation to changes in BMI and body weight. METHODS: We calculated a genetic risk score on the basis of 77 BMI-associated loci to determine the genetic susceptibility to obesity, and examined the interactions of changes in total and specific fruit and vegetable intake with the genetic risk score on changes in BMI and body weight within five 4-y intervals over 20 y of follow-up in 8943 women from the Nurses' Health Study (NHS) and 5308 men from the Health Professionals Follow-Up Study (HPFS). RESULTS: In the combined cohorts, repeated 4-y BMI change per 10-risk allele increment was 0.09 kg/m2 among participants with the greatest decrease in total fruit and vegetable intake and -0.02 among those with the greatest increase in intake (P-interaction <0.001; corresponding weight change: 0.20 kg compared with -0.06 kg). The magnitude of decrease in BMI associated with increasing fruit and vegetable intake was more prominent among participants with high genetic risk than those with low risk. Reproducible interactions were observed for fruits and vegetables separately (both P-interaction <0.001). Based on similar nutritional content, the interaction effect was greatest for berries, citrus fruits, and green leafy vegetables, and the interaction pattern persisted regardless of the different fiber content or glycemic load of fruits and vegetables. CONCLUSIONS: Genetically associated increased BMI and body weight could be mitigated by increasing fruit and vegetable intake, and the beneficial effect of improving fruit and vegetable intake on weight management was more pronounced in individuals with greater genetic susceptibility to obesity.

13.
Int J Mol Sci ; 20(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357654

RESUMO

The prevalence of obesity has been increasing markedly in the U.S. and worldwide in the past decades; and notably, the obese populations are signified by not only the overall elevated adiposity but also particularly harmful accumulation of body fat in the central region of the body, namely, abdominal obesity. The profound shift from "traditional" to "obesogenic" environments, principally featured by the abundance of palatable, energy-dense diet, reduced physical activity, and prolonged sedentary time, promotes the obesity epidemics and detrimental body fat distribution. Recent advances in genomics studies shed light on the genetic basis of obesity and body fat distribution. In addition, growing evidence from investigations in large cohorts and clinical trials has lent support to interactions between genetic variations and environmental factors, e.g., diet and lifestyle factors, in relation to obesity and body fat distribution. This review summarizes the recent discoveries from observational studies and randomized clinical trials on the gene-environment interactions on obesity and body fat distribution.

14.
Am J Clin Nutr ; 110(3): 750-758, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271198

RESUMO

BACKGROUND: A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM. OBJECTIVE: The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM. METHODS: We genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance. RESULTS: From baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of ß cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P = 0.03). CONCLUSIONS: The exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358.

15.
J Cell Physiol ; 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256427

RESUMO

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

16.
Nutr Metab Cardiovasc Dis ; 29(8): 793-801, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31248719

RESUMO

BACKGROUND AND AIMS: The insulin receptor substrate 1 (IRS1) rs2943650 was found to be associated with obesity in adults, but the association has not been evaluated in children. The present study aimed to examine whether IRS1 rs2943650 was associated with obesity in Chinese children and investigate the interaction between rs2943650 and physical activity. METHODS AND RESULTS: IRS1 rs2943650 was genotyped in 3303 Chinese children aged 6-18 years recruited from four independent studies. Logistic regression and linear regression were performed to examine associations. Meta-analyses were conducted to pool the results of the four independent studies. The C-allele carriers of rs2943650 showed a 29% higher risk of obesity than noncarriers (OR (95% CI) = 1.29 (1.05, 1.58), P = 0.02) and a 0.41 kg/m2 increase in BMI (ß (95% CI) = 0.41 (0.05, 0.78) kg/m2, P = 0.02). We also observed significant interactions between rs2943650 and physical activity/sedentary behaviors on obesity (Pforinteraction<0.05). Compared with the physically active children (physical activity ≥1 h/d and sedentary behaviors <2 h/d), the risk allele (C) of rs2943650 was significantly associated with a 241% increased risk of obesity among inactive children who participated in physical activity <1 h/d and sedentary behaviors ≥2 h/d (OR (95% CI) = 3.41 (1.45, 8.01), P = 0.005). CONCLUSIONS: We found that IRS1 rs2943650 was significantly associated with BMI and risk of childhood obesity. Additionally, we also found significant interaction between IRS1 rs2943650 polymorphism and physical activity/sedentary behaviors on childhood obesity. Our study would provide novel insights into the function of the IRS1 gene and the implementation of effective intervention strategies of childhood obesity.

17.
Curr Obes Rep ; 8(3): 262-283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31214942

RESUMO

PURPOSE OF REVIEW: This paper reviews the genetic and non-genetic factors that provided predictions of, or were associated with, weight loss and other metabolic changes in the POUNDS Lost clinical trial of weight loss. This trial randomized 811 individuals who were overweight or obese to one of four diets that contained either 15% or 25% protein and 20% or 40% fat in a 2 × 2 factorial design. A standard behavioral weight loss program was available for all participants who were followed for 2 years with an 80% completion rate. RECENT FINDINGS: Nineteen genes and five genetic risk scores were used along with demographic, behavioral, endocrine, and metabolic measurements. Genetic variations in most of the genes were associated with weight loss, but this association often varied with the dietary assignment. A number of demographic and behavioral factors, including attendance at behavioral sessions and food cravings were predictive of weight changes. A high baseline level of free triiodothyronine or free thyroxine predicted the magnitude of weight loss. Several perfluoroakyl compounds predicted more rapid weight regain. Genetic evidence from POUNDS Lost provides guidance toward selection of a personalized weight loss diet and improvement in metabolic profile. There is still room for additional research into the predictors of weight loss.

18.
Eur Heart J ; 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31216010

RESUMO

AIMS: Growing data suggest that antibiotic exposure is associated with a long-lasting alteration in gut microbiota, and may be related to subsequent cardiovascular disease (CVD). We investigated associations of life-stage and duration of antibiotic exposure during adulthood with subsequent CVD events. METHODS AND RESULTS: This study included 36 429 women initially free of CVD and cancer from the Nurses' Health Study. We estimated hazard ratios (HRs) for CVD (a composite endpoint of coronary heart disease or stroke) according to duration of antibiotic use in young (age 20-39), middle (age 40-59), and late (age 60 and older) adulthood. During an average of 7.6 years of follow-up, 1056 participants developed CVD. Women with long-term use of antibiotics (for ≥2 months) in late adulthood had a significantly increased risk of CVD (HR 1.32, 95% confidence interval 1.03-1.70) after adjustment for covariates (such as demographic factors, diet and lifestyle, reasons for antibiotic use, overweight or obesity, disease status, and other medication use), as compared to women who did not use antibiotics in this life-stage. Longer duration of antibiotic use in middle adulthood was also related to higher risk of CVD (P trend = 0.003) after controlling for these covariates. There was no significant relationship between the use in young adulthood and the risk of CVD. CONCLUSION: In this study which examined the antibiotic use in different life-stages, longer duration of exposure to antibiotics in the middle and older adulthood was related to an increased risk of future CVD events among elderly women at usual risk.

19.
Am J Clin Nutr ; 110(2): 473-484, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31190057

RESUMO

BACKGROUND: Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. OBJECTIVES: The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait. METHODS: We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963). RESULTS: In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095). CONCLUSIONS: Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle.

20.
Ren Fail ; 41(1): 446-454, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31162999

RESUMO

Objectives: Urine neutrophil gelatinase-associated lipocalin (NGAL) was found to increase in diabetic kidney disease (DKD). However, the clinical value of urine NGAL as diagnostic indicators in DKD remains to be clarified. Methods: Relevant studies were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. Stratified analyses and regression analyses were performed. Results: Fourteen studies with 1561 individuals were included in our analysis, including 1204 cross-sectional participants and 357 cohort participants. For the cross-sectional studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.82 (95% confidence interval (CI): 0.75-0.87) and 0.81 (95% CI: 0.68-0.90), respectively. The pooled diagnostic odds ratio was 19 (95% CI: 11-33), and the overall area under the curve was 0.88 (95% CI: 0.84-0.90). For the cohort studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.96 (95% CI: 0.91-0.98) and 0.89 (95% CI: 0.84-0.92), respectively. The overall area under the curve was 0.98, indicating good discriminative ability of NGAL as biomarkers for DKD. Conclusions: Urine NGAL, as the early diagnostic marker of DKD, might have the high diagnostic value, especially in cohort studies.

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