Background:
Inflammation is implicated in the etiology of various aging-related diseases. Numerous dietary and lifestyle factors contribute to chronic systemic inflammation; genetic variation may ...too. However, despite biological plausibility, little is known about associations of antioxidant enzyme (AE) and DNA base excision repair (BER) genotypes with human systemic inflammation.
Methods:
We genotyped 22 single nucleotide polymorphisms (SNPs) in 3 AE genes, and 79 SNPs in 14 BER genes to develop inflammation-specific AE and BER genetic risk scores (GRS) in two pooled cross-sectional studies (
n
= 333) of 30–74-year-old White adults without inflammatory bowel disease, familial adenomatous polyposis, or a history of cancer or colorectal adenoma. Of the genotypes, based on their associations with a biomarker of systemic inflammation, circulating high sensitivity C-reactive protein (hsCRP) concentrations, we selected 2 SNPs of 2 genes (
CAT
and
MnSoD
) for an AE GRS, and 7 SNPs of 5 genes (
MUTYH
,
SMUG1
,
TDG
,
UNG
, and
XRCC1
) for a BER GRS. A higher GRS indicates a higher balance of variant alleles directly associated with hsCRP relative to variant alleles inversely associated with hsCRP. We also calculated previously-reported, validated, questionnaire-based dietary (DIS) and lifestyle (LIS) inflammation scores. We used multivariable general linear regression to compare mean hsCRP concentrations across AE and BER GRS categories, individually and jointly with the DIS and LIS.
Results:
The mean hsCRP concentrations among those in the highest relative to the lowest AE and BER GRS categories were, proportionately, 13.9% (
p
= 0.30) and 57.4% (
p
= 0.009) higher. Neither GRS clearly appeared to modify the associations of the DIS or LIS with hsCRP.
Conclusion:
Our findings suggest that genotypes of DNA BER genes collectively may be associated with systemic inflammation in humans.
Associations between individual foods or nutrients and oxidative markers have been reported. Comprehensive measures of food intake may be uniquely informative, given the complexity of oxidative ...systems and the possibility of antioxidant synergies. We quantified associations over a 20-year history between three food-based dietary patterns (summary measures of whole diet) and a plasma biomarker of lipid peroxidation, F2-isoprostanes, in a cohort of Americans ages 18–30 at year 0 (1985–1986). We assessed diet at years 0, 7, and 20 through a detailed history of past-month food consumption and supplement use and measured plasma F2-isoprostanes at years 15 and 20. We created three dietary patterns: (1) a priori (“a priori diet quality score”) based on hypothesized healthfulness of foods, (2) an empirical pattern reflecting high fruit and vegetable intake (“fruit–veg”), and (3) an empirical pattern reflecting high meat intake (“meat”). We used linear regression to estimate associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718), adjusting for age, sex, race, total energy intake, education, smoking, body mass index, waist circumference, physical activity, and supplement use. In multivariable-adjusted cross-sectional analysis, the a priori diet quality score and the fruit–veg diet pattern were negatively, and the meat pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations remained statistically significant in prospective analysis. Our findings suggest that long-term adherence to a diet rich in fruits and vegetables and low in red meat may decrease lipid peroxidation.
► Summary measures of diet were associated with plasma F2-isoprostanes. ► Plant-based diets were associated with lower lipid peroxidation. ► Supplement use and dietary antioxidant nutrients did not account for findings.
Identification of the mechanisms involved in the pathology of nutrient deficiency provides an understanding of nutrient functions, their role in metabolism, and interactions between nutrients. ...However, evidence has emerged in recent years that low (suboptimal) intakes of micronutrients are associated with an elevated risk of chronic diseases. The description of micronutrient associations with chronic disease as a deficiency disease does not capture the complexity of these relations. It implies a significant oversimplification of this relation and detracts from the need for development of new approaches to this area of study. Epidemiologic study designs are essential for progress in understanding the micronutrient-chronic-disease relations, and these are described. Two areas wherein epidemiological tools could be incorporated into experimental designs have been vitamin D and prostate cancer, and vitamin D and colon cancer. In each case, biomarkers of exposure, intermediary markers, and mechanisms have been identified and could be implemented in new experimental designs. Measures of exposure would be improved by incorporation of measurements of vitamin D status such as serum 25-hydroxyvitamin D measurements. Several intermediary markers are discussed and may be useful in the characterization of responses. Such developments should aid in the interpretation of studies and identify vitamin D, as well as calcium intakes, that will aid in the prevention of prostate and colon cancer.
Purpose
To examine the association between soy products and their components, isoflavones and protein, and incident type 2 diabetes in a population with varied soy intake and high rates of diabetes.
...Methods
We used data from the Singapore Chinese Health Study, including 43,176 Chinese men and women aged 45–74 years, free of chronic disease at baseline (1993–1998) and followed through 2004. Intake of individual soy items, total unsweetened soy, and soy components was assessed by food-frequency questionnaire and examined with type 2 diabetes risk using Cox regression.
Results
During an average follow-up of 5.7 years, 2,252 of the 43,176 participants included in the current analyses developed diabetes. After adjustment for potential confounders and BMI, consumption of unsweetened soy was inversely associated with diabetes risk. Hazard ratios (HRs) and 95% CI for diabetes across unsweetened soy intake categories (none, 1–4/month, 1–2/week, 3–4/week, ≥5/week) were: 1 (referent), 0.81 (0.67–0.97), 0.76 (0.63–0.91), 0.76 (0.63–0.92), and 0.72 (0.59–0.89), respectively (
P
trend
= 0.015). Conversely, in multivariate models, consuming sweetened soybean drink was positively associated with diabetes risk. HRs for diabetes across soybean drink intake categories (none, 1–3/month, 1/week, ≥2/week) were: 1 (referent), 1.07 (0.95–1.20), 1.12 (1.00–1.26), and 1.13 (1.00–1.28), respectively (
P
trend
= 0.03). Furthermore, after full adjustment, including adjustment for sweetened soy items, we observed a marginally significant inverse association between isoflavone intake and diabetes (HR for the fifth compared to the first quintile: 0.76; 95% CI: 0.58–1.00;
P
trend
= 0.08).
Conclusions
The current findings support a protective role for unsweetened soy foods and isoflavones on risk of type 2 diabetes.
Several epidemiological studies have demonstrated that carotenoid concentrations relate inversely to cardiovascular disease incidence. Thus, we examined the association of circulating carotenoids ...with hypertension, a major macrovascular disease risk factor.
Black and White men and women in the Coronary Artery Risk Development in Young Adults Study, aged 18-30 years at recruitment (1985-1986) from four US cities, were investigated over 20 years. At years 0, 7, and 15, we determined the relationships of the sum of four serum carotenoids (alpha-carotene, beta-carotene, lutein/zeaxanthin, cryptoxanthin) and of lycopene with incident hypertension using proportional hazards regression models.
In 4412 participants, year 0 sum of four carotenoids was significantly inversely associated with 20-year hypertension incidence after adjustment for baseline systolic blood pressure and other confounding factors (relative hazard per SD increase of sum of four carotenoids: 0.91; 95% confidence interval = 0.84-0.99). The inverse relationships persisted in time-dependent models updating year 0 sum of four carotenoids with year 7 and year 15 values (relative hazard per SD increase of sum of four carotenoids: 0.84; 95% confidence interval = 0.77-0.92). Lycopene was unrelated to hypertension in any model.
Those individuals with higher concentrations of sum of carotenoids, not including lycopene, generally had lower risk for future hypertension.
BACKGROUND: Consumption of plant foods and dairy and meat products may moderate increases in blood pressure. OBJECTIVE: The objective was to evaluate associations of dietary intake with the 15-y ...incidence of elevated blood pressure (EBP; ie, incident systolic BP >/= 130 mm Hg, diastolic BP >/= 85 mm Hg, or use of antihypertensive medication). DESIGN: Proportional hazards regression was used to evaluate relations of dietary intake at years 0 and 7 with the 15-y incidence of EBP in the Coronary Artery Risk Development in Young Adults (CARDIA) Study of 4304 participants aged 18-30 y at baseline. RESULTS: EBP incidence varied from 12% in white women to 33% in black men. Plant food intake (whole grains, refined grains, fruit, vegetables, nuts, or legumes) was inversely related to EBP after adjustment for age, sex, race, center, energy intake, cardiovascular disease risk factors, and other potential confounding factors. Compared with quintile 1, the relative hazards of EBP for quintiles 2-5 of plant food intake were 0.83 (95% CI: 0.68, 1.01), 0.83 (0.67, 1.02), 0.82 (0.65, 1.03), and 0.64 (0.53, 0.90), respectively; P for trend = 0.01. Dairy intake was not related to EBP (P for trend = 0.06), and positive dose-response relations for EBP were observed across increasing quintiles of meat intake (P for trend = 0.004). In subgroup analyses, risk of EBP was positively associated with red and processed meat intake, whereas it was inversely associated with intakes of whole grain, fruit, nuts, and milk. Adjustment for intermediary factors in the causal pathway attenuated these relations. CONCLUSION: These findings are consistent with a beneficial effect of plant food intake and an adverse effect of meat intake on blood pressure.
BACKGROUNDAtrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation ...while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease.
METHODSIn a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45–84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65–84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset.
RESULTSBaseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 1.94–4.08 for PIIINP ≥8.5 µg/L 3.5% of the sample and 3.46 2.36–5.07 for ICTP ≥7 µg/L 1.7% of the sample). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions.
CONCLUSIONSPlasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.
Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene ...expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV
), Forced Vital Capacity (FVC) and FEV
/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study. Spirometry testing was used to measure lung function and gene expression levels were measured using the Nanostring platform. Multivariate linear regression models were used to study the association between lung function measured at year 30, 10-year decline from year 20 to year 30, and gene expression levels (highest quartile divided into two levels - 75th to 95th and>95th to 100th percentile) adjusting for center, smoking and BMI, measured at year 25. Year 30 FEV
and FVC were lower in the highest level of TLR5 compared to the lowest quartile with difference of 4.00% (p for trend: 0.04) and 3.90% (p for trend: 0.05), respectively. The 10-year decline of FEV
was faster in the highest level of CCR1 as compared to the lowest quartile with a difference of 1.69% (p for trend: 0.01). There was no association between gene expression and FEV
/FVC. Higher gene expression levels in TLR5 and CCR1 are associated with lower lung function and faster decline in FEV
over 10 years, in a threshold manner, providing new insights into the role of inflammation in lung function.
The authors examined the association between circulating 25-hydroxyvitamin D3 (25(OH)D3), the best indicator of total vitamin D exposure, and incident, sporadic colorectal adenoma risk in a pooled ...analysis of primary data from 3 colonoscopy-based case-control studies conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. The pooled study included 616 colorectal adenoma cases and 770 polyp-free controls. Multivariable logistic regression was used to estimate the association between circulating 25(OH)D3 and colorectal adenoma risk. Stratified analyses and the likelihood ratio test were used to examine effect modification by various risk factors. In the pooled analysis, higher circulating 25(OH)D3 concentrations were statistically significantly associated with decreased colorectal adenoma risk (highest vs. lowest quartile odds ratio = 0.59, 95% confidence interval: 0.41, 0.84). The observed inverse association was stronger among participants who used nonsteroidal antiinflammatory drugs regularly (highest vs. lowest quartile odds ratio = 0.33, 95% confidence interval: 0.19, 0.56). Inverse associations between 25(OH)D3 and colorectal adenoma did not differ substantially by other risk factors or by adenoma characteristics. These findings support the hypothesis that greater vitamin D exposure may reduce the risk of colorectal adenoma and suggest that it may do so more strongly in combination with antiinflammatory agents.
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