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1.
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.

2.
Circ Res ; 125(9): 824-833, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510868

RESUMO

RATIONALE: Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking. OBJECTIVE: To identify 5'-cytosine-phosphate-guanine-3' in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort. METHODS AND RESULTS: Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (PFDR <0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (P<0.001 both in blacks and in whites). CONCLUSIONS: The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.

3.
Aging (Albany NY) ; 11(16): 5895-5923, 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31422385

RESUMO

Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.

4.
Aging (Albany NY) ; 11(16): 5876-5894, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31461406

RESUMO

Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P<1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

5.
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.

6.
BMJ ; 366: l4292, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345923

RESUMO

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Adulto , Alelos , Diabetes Mellitus Tipo 2/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
7.
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.

8.
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.

9.
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.

10.
BMJ ; 365: l1628, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088786

RESUMO

OBJECTIVE: To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. DESIGN: Prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: 466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. MAIN OUTCOME MEASURES: Incident CVD events, including CVD death, coronary heart disease, and stroke. RESULTS: During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00). CONCLUSION: Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.


Assuntos
Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais , Glucosamina/uso terapêutico , Dor/prevenção & controle , Doença das Coronárias/epidemiologia , Seguimentos , Humanos , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Reino Unido/epidemiologia
11.
Ocul Surf ; 17(3): 470-475, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31015041

RESUMO

PURPOSE: Submandibular gland (SMG) transplantation improves the tear film and other ocular-surface features for patients with severe dry eye disease (DED). Using the dry eye-related quality of life (QOL) questionnaire, we aimed to evaluate whether DED patients' QOL would benefit from SMG transplantation and determine whether preoperative ophthalmologic and QOL measurements could predict which patients would be most satisfied with this surgery. METHODS: This prospective study included DED patients with successful SMG transplantation. Using the Chinese version of the Dry Eye Related Quality of Life (CDERQOL) instrument, QOL was measured before and 1-year after surgery. RESULTS: The QOL data of 51 consecutive patients were analyzed. Before surgery, all the patients had a poor QOL. One year after surgery, all five QOL domains (Dry Eye Symptom Bother, Impact on Daily Activities, Emotional Impact, Impact on Work, and Satisfaction with Treatment) showed significant improvement (P < 0.01). Unsuccessful treatment experience with cyclosporin eyedrops as well as pre-surgical low scores of visual acuity and all five QOL domains (except for "Satisfaction with Treatment") were found to significantly increase the post-surgical QOL scores (P < 0.01); however, pre-surgical Schirmer's test, break-up times of tear-film, and corneal fluorescein staining measurements showed no effects or contradictory correlations with post-surgical QOL scores. CONCLUSION: The life quality and satisfaction of DED patients showed significant improvement after SMG transplantation. Patients with severe and refractory DED could reap the benefits of surgery. A subjective QOL questionnaire is very valuable for predicting and evaluating the treatment effect.

12.
Circ Res ; 124(6): 930-937, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646822

RESUMO

RATIONALE: In observational studies, type 2 diabetes mellitus (T2D) has been associated with an increased risk of hypertension, and vice versa; however, the causality between these conditions remains to be determined. OBJECTIVES: This population-based prospective cohort study sought to investigate the bidirectional causal relations of T2D with hypertension, systolic and diastolic blood pressure (BP) using Mendelian randomization (MR) analysis. METHODS AND RESULTS: After exclusion of participants free of a history of heart failure, cardiovascular disease, cardiac procedures, and non-T2D diabetes mellitus, a total of 318 664 unrelated individuals with qualified genotyping data of European descent aged 37 to 73 from UK Biobank were included. The genetically instrumented T2D and hypertension were constructed using 134 and 233 single nucleotide polymorphisms, respectively. Seven complementary MR methods were applied, including inverse-variance weighted method, 2 median-based methods (simple and weighted), MR-Egger, MR-robust adjusted profile scores, MR-Pleiotropy Residual Sum and Outlier, and multivariate MR. The genetically instrumented T2D was associated with risk of hypertension (odds ratio, 1.07 [95% CI, 1.04-1.10], P=3.4×10-7), whereas the genetically determined hypertension showed no relationship with T2D (odds ratio, 0.96 [0.88-1.04], P=0.34). Our MR estimates from T2D to BP showed that the genetically instrumented T2D was associated with a 0.67 mm Hg higher systolic BP (95% CI, 0.41-0.93, P=5.75×10-7) but not with a higher diastolic BP. There was no clear evidence showing a causal effect of elevated systolic BP or diastolic BP on T2D risk. Positive pleiotropic bias was indicated in the hypertension→T2D relation (odds ratio, of MR-Egger intercept 1.010 [1.004-1.016], P=0.001) but not from T2D to hypertension (1.001 [0.998-1.004], P=0.556). CONCLUSIONS: T2D may causally affect hypertension, whereas the relationship from hypertension to T2D is unlikely to be causal. These findings suggest the importance of keeping an optimal glycemic profile in general populations, and BP screening and monitoring, especially systolic BP, in patients with T2D.

13.
Am J Clin Nutr ; 109(3): 665-673, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30629107

RESUMO

BACKGROUND: A growing amount of data suggests that n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change. OBJECTIVES: We aimed to prospectively test interactions of habitual consumption of n-3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change. DESIGN: Gene-diet interactions were examined in 11,330 women from the Nurses' Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI). RESULTS: In the NHS and HPFS cohorts, food-sourced long-chain n-3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction = 0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction = 0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and -0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n-3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction = 0.01), NHS (P-interaction = 0.03), WHI (P-interaction = 0.10), and the combined cohorts (P-interaction = 0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, -0.08, and -0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction = 0.003) and long-chain n-3 PUFA intake (P-interaction = 0.12). CONCLUSION: Our study provides replicable evidence to show that high intakes of fish and long-chain n-3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.

14.
Am J Clin Nutr ; 108(5): 1129-1134, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475961

RESUMO

Background: Obesity is closely associated with bone health. Although diet and weight loss produce many metabolic benefits, studies of weight loss diets on bone health are conflicting. Genetic variations, such as vitamin D levels, may partly account for these conflicting observations by regulating bone metabolism. Objective: We investigated whether the genetic variation associated with vitamin D concentration affected changes in bone mineral density (BMD) in response to a weight-loss diet intervention. Design: In the 2-y Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, BMD was measured for 424 participants who were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A genetic risk score (GRS) was calculated based on 3 genetic variants [i.e., 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657 and group-specific component globulin (GC) rs2282679] related to circulating vitamin D levels. A dual-energy X-ray absorptiometry scan was performed to assess changes in whole-body BMD over 2 y. The final analysis included 370 participants at baseline. Results: We found a significant interaction between dietary fat intake and vitamin D GRS on 2-y changes in whole-body BMD (P-interaction = 0.02). In the high-fat diet group, participants with higher GRS showed significantly less reduction in whole-body BMD than those with lower GRS, whereas the genetic associations were not significant in the low-fat diet group. We also found a significant interaction between dietary fat intake and the GRS on 6-mo change in femur neck BMD (P-interaction = 0.02); however, the interaction became nonsignificant at 2 y. Conclusion: Our data indicate that dietary fat intake may modify the effect of vitamin D-related genetic variation on changes in BMD. Overweight or obese patients predisposed to sufficient vitamin D may benefit more in maintaining BMD along with weight loss by eating a low-fat diet. This trial was registered at clinicaltrials.gov as NCT03258203.

15.
Gut ; 2018 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-29860242

RESUMO

OBJECTIVE: Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. DESIGN: We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. RESULTS: Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. CONCLUSION: Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. TRIAL REGISTRATION NUMBER: NCT00072995.

16.
Int J Obes (Lond) ; 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29777237

RESUMO

BACKGROUND: Growing evidence has implicated DNA methylation (DNAm) in the regulation of body adiposity; a recent epigenome-wide association study (EWAS) identified a genetic variant determining DNAm at the SREBF1 gene that affected body mass index (BMI). OBJECTIVE: In the present study, we tested interactions between DNAm variant rs752579 and methylation metabolism-related B-vitamins (folate, vitamin B2, vitamin B6, and vitamin B12) on longitudinal change in BMI in the Women's Health Initiative Memory Study (WHIMS). DESIGN: A total of 5687 white women aged 65-79 from WHIMS with genotyping data on SNP rs752579 were included in the analysis. B-vitamins intakes were estimated by a self-report semi-quantitative food frequency questionnaire. BMI was measured at baseline and 6-year follow-up. RESULT: We found significant interactions between the SREBF1 rs752579 genotype and intake of food source B-vitamins on 6-year change in BMI (p interaction <0.01 for all). BMI changes (kg/m2) per DNAm-increasing (C) allele were -0.29, 0.06, and 0.11 within subgroups of increasing tertiles of food source folate intake; and the corresponding BMI changes (kg/m2) were -0.25, -0.01, and 0.15 for vitamin B2 intake; -0.17, -0.16, and 0.21 for vitamin B6 intake; and -0.12, -0.23, and 0.26 for vitamin B12 intake, respectively. Similar gene-diet interaction patterns were observed on the change in body weight. CONCLUSIONS: Our data suggest that habitual intake of food source B-vitamins may modify the effect of DNAm-related variant on long-term adiposity change.

17.
J Gastroenterol Hepatol ; 33(11): 1925-1931, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29671893

RESUMO

BACKGROUND AND AIM: Gallstone disease has been related to a higher prevalence and incidence of chronic conditions, such as dyslipidemia, obesity, and cardiovascular disease (CVD). However, limited data are available regarding whether gallstone disease is related to mortality. METHODS: We examined the relationship of a history of gallstone disease and risk of death, using Cox proportional hazards regression analysis, among 86 030 women from the Nurses' Health Study and 43 949 men from the Health Professionals Follow-up Study. RESULTS: During the up-to 32 years of follow-up, 34 011 all-cause deaths were confirmed, of which 8138 were CVD deaths and 12 173 were cancer deaths. For the participants with a history of gallstone disease compared with those without, the hazard ratio of total mortality was 1.16 (95% confidence interval 1.13, 1.20), of CVD mortality 1.11 (1.05, 1.17), of cancer mortality 1.15 (1.09, 1.20), and of other mortality 1.19 (1.14, 1.25) from a pooled-analysis of women and men (all P < 0.001). The multi-adjusted associations between gallstone disease and total mortality persisted among women and men, and among participants with various risk profiles including the different status of body mass index, hormone therapy use, diabetes, hypertension, and hypercholesterolemia (all P for interaction ≥ 0.09). CONCLUSION: These data suggest that gallstone disease is associated with a higher risk of total mortality and disease-specific mortality, including CVD and cancer mortality, independent of various traditional risk factors.


Assuntos
Cálculos Biliares/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Doença Crônica , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Feminino , Seguimentos , Cálculos Biliares/complicações , Humanos , Incidência , Masculino , Neoplasias/mortalidade , Obesidade/epidemiologia , Obesidade/etiologia , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
18.
Diabetes Obes Metab ; 20(9): 2298-2303, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29693310

RESUMO

DNA Methylation of NFATC2IP was recently identified as being causally related to body mass index. The present study aimed to examine the roles of the genetic variation, methylation and gene expression at this locus in adiposity changes in a 2-year weight-loss trial. Participants (n = 692) were genotyped and randomly assigned to 1 of the 4 reduced-calorie diets, DNA methylation was derived from stored blood samples at baseline (n = 48), and adipose tissue gene expression was measured in 96 volunteers. We found significant interactions of fat intake with the genetic (rs11150675) and transcriptional (ILMN_1725441) variations at the NFATC2IP locus on 2-year weight change (Pinteraction < .01). Similarly, cis-DNA methylation at cg26663590 of the NFATC2IP locus showed an opposite impact on weight-loss in response to high-fat vs low-fat diet (effect size, 4.62 vs -1.24 kg). Additionally, baseline methylation at cg26663590 causally mediated 52.8% of the effect of rs11150675 on 2-year weight-loss in the high-fat diet group (P = .01), whereas no such mediation was observed in the low-fat diet group. Our findings suggest potentially causal effects of genetic, epigenetic and transcriptional variations at the NFATC2IP locus on adiposity changes in response to dietary fat intake.

19.
Hypertension ; 71(5): 928-936, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29632104

RESUMO

Asthma is related to various cardiovascular risk. Whether a history of asthma from childhood contributes to arterial stiffness in adulthood, a noninvasive surrogate for cardiovascular events, is unknown. Prospective analyses were performed among 1746 Bogalusa Heart Study participants aged 20 to 51 years with data on self-report asthma collected since childhood. Aorta-femoral pulse wave velocity (af-PWV, m/s) was repeatedly assessed among adults ≥aged 18 years. Generalized linear mixed models and generalized linear models were fitted for the repeated measurements of af-PWV and its changes between the last and the first measurements, respectively. After a median follow-up of 11.1 years, participants with a history of asthma from childhood had a higher af-PWV (6.78 versus 6.13; P=0.048) and a greater increase in af-PWV (8.99 versus 2.95; P=0.043) than those without asthma, adjusted for age, sex, race, smoking status, heart rate, body mass index, systolic blood pressure, lipids, and glycemia. In addition, we found significant interactions of asthma with body mass index and systolic blood pressure on af-PWV and its changes (P for interaction <0.01). The associations of asthma with af-PWV and its changes appeared to be stronger among participants who were overweight and obese (body mass index ≥25 kg/m2) or with prehypertension and hypertension (systolic blood pressure ≥120 mm Hg) compared with those with a normal body mass index or systolic blood pressure. Our findings indicate that a history of asthma from childhood is associated with higher af-PWV and greater increases in af-PWV, and such associations are stronger among young adults who are overweight or with elevated blood pressure.

20.
Eur J Nutr ; 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29516223

RESUMO

PURPOSE: A common variant of the melatonin receptor 1B (MTNR1B) gene has been related to increased signaling of melatonin, a hormone previously associated with body fatness mainly through effects on energy metabolism. We examined whether the MTNR1B variant affects changes of body fatness and composition in response to a dietary weight loss intervention. METHODS: The MTNR1B rs10830963 variant was genotyped for 722 overweight and obese individuals, who were randomly assigned to one of four diets varying in macronutrient composition. Anthropometric and body composition measurements (DXA scan) were collected at baseline and at 6 and 24 months of follow-up. RESULTS: Statistically significant interactions were observed between the MTNR1B genotype and low-/high-fat diet on changes in weight, body mass index (BMI), waist circumference (WC) and total body fat (p interaction = 0.01, 0.02, 0.002 and 0.04, respectively), at 6 months of dietary intervention. In the low-fat diet group, increasing number of the sleep disruption-related G allele was significantly associated with a decrease in weight (p = 0.004), BMI (p = 0.005) and WC (p = 0.001). In the high-fat diet group, carrying the G allele was positively associated with changes in body fat (p = 0.03). At 2 years, the associations remained statistically significant for changes in body weight (p = 0.02), BMI (p = 0.02) and WC (p = 0.048) in the low-fat diet group, although the gene-diet interaction became less significant. CONCLUSIONS: The results suggest that carriers of the G allele of the MTNR1B rs10830963 may have a greater improvement in body adiposity and fat distribution when eating a low-fat diet.

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