Shared environmental factors associated with telomere length maintenance in elderly male twins

During aging, chromosome ends, or telomeres, gradually erode or shorten with each somatic cell division. Loss of telomere length homeostasis has been linked to age-related disease. Remarkably, specific environmental assaults, both physical and psychological, have been shown to correlate with shortened telomeres. However, the extent that genetic and/or environmental factors may influence telomere length during later stages of lifespan is not known. Telomere length was measured in 686 male US World War II and Korean War veteran monozygotic (MZ) and dizygotic (DZ) twins (including 181 MZ and 125 DZ complete pairs) with a mean age of 77.5 years (range 73-85 years). During the entire process of telomere length measurement, participant age and twin status were completely blinded. White blood cell mean telomere length shortened in this elderly population by 71 base pairs per year (P < 0.0001). We observed no evidence of heritable effects in this elderly population on telomere length maintenance, but rather find that telomere length was largely associated with shared environmental factors (P < 0.0001). Additionally, we found that individuals with hypertension and cardiovascular disease had significantly shorter telomeres (P = 0.0025 and 0.002, respectively). Our results emphasize that shared environmental factors can have a primary impact on telomere length maintenance in elderly humans.     

Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study

Background

Poor muscular strength has been shown to be associated with increased morbidity and mortality in diverse samples of middle-aged and elderly people. However, the oldest old population (i.e., over 85 years) is underrepresented in such studies. Our objective was to assess the association between muscular strength and mortality in the oldest old population.

Methods

We included 555 participants (65% women) from the Leiden 85-plus study, a prospective population-based study of all 85-year-old inhabitants of Leiden, Netherlands. We measured the handgrip strength of participants at baseline and again at age 89 years. We collected baseline data on comorbidities, functional status, levels of physical activity, and adjusted for potential confounders. During the follow-up period, we collected data on mortality.

Results

During a follow-up period of 9.5 years (range 8.5–10.5 years), 444 (80%) participants died. Risk for all-cause mortality was elevated among participants in the lowest tertile of handgrip strength at age 85 years (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.00–1.82, p = 0.047) and the lowest two tertiles of handgrip strength at age 89 years (HR 2.04, CI 1.24–3.35, p = 0.005 and HR 1.73, CI 1.11–2.70, p = 0.016). We also observed significantly increased mortality among participants in the tertile with the highest relative loss of handgrip strength over four years (HR 1.72, CI 1.07–2.77, p = 0.026).

Interpretation

Handgrip strength, a surrogate measurement of overall muscular strength, is a predictor of all-cause mortality in the oldest old population and may serve as a convenient tool for prognostication of mortality risk among elderly people.The fastest growing segment of the elderly population is the group older than 85 years, which is classified as the oldest old age group.^1,2 The average rate of growth of this group is reported to be 3.8% annually at a global level. By 2050, the oldest old age group will account for one-fifth of all older persons.²Inactivity is a major problem in this age group, owing to an increased prevalence of medical comorbidities and physical disability with age. Age-related stereotypes and misconceptions (e.g., that older people are invariably unhealthy), coupled with a perceived lack of benefits provided by physical activity, can also represent obstacles to exercise among the oldest old population.The predisposing influence of a sedentary lifestyle on age-related cardiometabolic diseases (i.e., obesity, type 2 diabetes mellitus, hypertension and coronary artery disease) is well established. Evidence of the protective effects of physical activity against certain cancers, falls and mental health problems is accumulating.^3,4 Lack of exercise is also a significant risk factor for sarcopenia,^5,6 a progressive loss of skeletal muscle mass and strength with aging.⁷ Sarcopenia is highly prevalent among those aged 80 years and older, with reported rates exceeding 50%.⁸ Reduced muscular strength is associated in turn with outcomes such as physical disability,^9,10 cognitive decline¹¹ and mortality.^12,13Handgrip strength, a simple bedside tool, has been shown to be a valid surrogate measurement of overall muscular strength.^14,15 A recent systematic review has shown that low handgrip strength is associated consistently with premature mortality, disability and other health-related complications among various samples of middle-aged and older people.¹⁶ Despite its prognostic value, handgrip dynamometry is rarely used in routine geriatric assessment. Epidemiologic studies evaluating the relation in the population of the oldest old are also lacking. We tested the association between handgrip strength and mortality in a prospective population-based study of the oldest old age group. We obtained approval for our study from the Medical Ethical Committee of the Leiden University Medical Center, and informed consent from all participants.     

New-onset atrial fibrillation in sepsis is associated with increased morbidity and mortality

BackgroundThe development of new-onset atrial fibrillation in sepsis has been associated with adverse outcomes.MethodsA systematic literature search was conducted to retrieve articles that investigated the association of new-onset atrial fibrillation in patients diagnosed with sepsis. The primary outcome of interest was the pooled risk ratio (RR) of in-hospital mortality in patients with new-onset atrial fibrillation and sepsis.ResultsSix studies included 3100 patients with new-onset atrial fibrillation in sepsis and 36,900 patients without new-onset atrial fibrillation in sepsis. The pooled RR for in-hospital mortality was 1.45 (95 % CI 1.32–1.60, p < 0.00001, I^2 =24 %). New-onset atrial fibrillation was also associated with increased ICU mortality, ICU and in-hospital length of stay and stroke. New-onset atrial fibrillation occurred more in the elderly, those with a prior history of cardiovascular and respiratory disease, and those with increased severity of illness.ConclusionProspective randomised trials are needed to clarify the significance of new-onset atrial fibrillation in sepsis, optimal treatment strategies for these patients, and the benefit of systemic anticoagulation. Physicians should be aware that new-onset atrial fibrillation in sepsis is not merely an observed temporary arrhythmia but a marker of poor prognosis and should be managed accordingly.     

avpr1a length polymorphism is not associated with either social or genetic monogamy in free-living prairie voles

Recent discoveries of single-gene influences on social behaviour have generated a great deal of interest in the proximate mechanisms underlying the expression of complex behaviours. Length polymorphism in a microsatellite in the regulatory region of the gene encoding the vasopressin 1a receptor (avpr1a) has been associated with both inter- and intra-specific variation in socially monogamous behaviour in voles (genus Microtus) under laboratory conditions. Here, we evaluate the relationship between avpr1a length polymorphism and social associations, genetic monogamy, and reproductive success in free-living prairie vole (M. ochrogaster) populations. We found no evidence of a relationship between avpr1a microsatellite length and any of our correlates of either social or genetic monogamy in the field. Our results, especially when taken in conjunction with those of recent experimental studies in semi-natural enclosures, suggest that avpr1a polymorphism is unlikely to have been a major influence in the evolution or maintenance of social monogamy in prairie voles under natural conditions.     

Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study

Background

The Sykes' monkey and related forms (Cercopithecus mitis) make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk). We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western blot assay and analyzed the data by origin, subspecies, age and sex.

Results

The SIVsyk antigen-specific Western blot assay detected more serum samples as positive than either of the cross-reactive ELISA assays. Using this assay, we found that seroprevalence is higher than previously reported, but extremely variable in wild populations (from 0.0 to 90.9%). Females were infected more often than males in both wild and captive populations. Seropositive infants were common. However, no seropositive juveniles were identified.

Conclusion

We have developed a specific and sensitive Western blot assay for anti-SIVsyk antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with extremely variable prevalence in the wild. Higher infection prevalence in females suggests predominantly sexual transmission. High infection prevalence in infants, but none in juveniles, suggests maternal antibodies, but little or no vertical transmission.     

Cytomegalovirus seropositivity is associated with glucose regulation in the oldest old. Results from the Leiden 85-plus Study

ABSTRACT: BACKGROUND: Cytomegalovirus (CMV) infection has been reported to contribute to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, CMV infection has not been evaluated as a possible risk factor for type 2 diabetes. Our aim was to investigate potential associations between CMV seropositivity, CMV IgG antibody level and glucose regulation in the oldest old. RESULTS: CMV seropositive subjects were more likely to have type 2 diabetes (17.2% vs 7.9%, p = 0.016), had a higher level of HbA1c (p = 0.014) and higher non-fasting glucose (p = 0.024) in the oldest olds. These associations remained significant after adjustment for possible confounders. CMV IgG antibody level was not significantly associated with glucose regulation (all p > 0.05). CONCLUSIONS: In the oldest old, CMV seropositivity is significantly associated with various indicators of glucose regulation. This finding suggests that CMV infection might be a risk factor for the development of type 2 diabetes in the elderly.     

The bias associated with the dispersion of length at age in the estimation of growth and mortality parameters from uni-modal length-frequency data

Values of M and M/K extracted from simulated uni-modal length-frequency data representing 28 fish stocks were biased. The bias exceeded 20% when the life span of the stock was <5 or >15 years.     

Telomere length is associated with types of chromosome 21 nondisjunction: a new insight into the maternal age effect on Down syndrome birth

Advanced maternal age is a well-documented risk factor of chromosome 21 nondisjunction in humans, but understanding of this association at the genetic level is still limited. In particular, the state of maternal genetic age is unclear. In the present study, we estimated maternal genetic age by measuring telomere length of peripheral blood lymphocytes among age-matched mothers of children with Down syndrome (cases: N = 75) and mothers of euploid children (controls: N = 75) in an age range of 18–42 years. All blood samples were taken within 1 week of the birth of the child in both cases and controls. The telomere length estimation was performed by restriction digestion—Southern blot hybridization method. We stratified the cases on the basis of centromeric STR genotyping into maternal meiosis I (N = 48) and maternal meiosis II (N = 27) nondisjunction groups and used linear regression to compare telomere length as a function of age in the euploid, meiosis I and meiosis II groups. Our results show that all three groups have similar telomere length on average for younger mothers. As age increases, all groups show telomere loss, but that loss is largest in the meiosis II mother group and smallest in the euploid mother group with the meiosis I mother group in the middle. The regression lines for all three were statistically significantly different from each other (p < 0.001). Our results do not support the theory that younger women who have babies with Down syndrome do so because are ‘genetically older’ than their chronological age, but we provide the first evidence that older mothers who have babies with Down syndrome are “genetically older” than controls, who have euploid babies at the same age. We also show for the first time that telomere length attrition may be associated in some way with meiosis I and meiosis II nondisjunction of chromosome 21 and subsequent Down syndrome births at advanced maternal age.     

Exogenous visual orienting is associated with specific neurotransmitter genetic markers: a population-based genetic association study

Background

Currently, there is a sense that the spatial orienting of attention is related to genotypic variations in cholinergic genes but not to variations in dopaminergic genes. However, reexamination of associations with both cholinergic and dopaminergic genes is warranted because previous studies used endogenous rather than exogenous cues and costs and benefits were not analyzed separately. Examining costs (increases in response time following an invalid pre-cue) and benefits (decreases in response time following a valid pre-cue) separately could be important if dopaminergic genes (implicated in disorders such as attention deficit disorder) independently influence the different processes of orienting (e.g., disengage, move, engage).

Methodology/Principal Findings

We tested normal subjects (N = 161) between 18 and 61 years. Participants completed a computer task in which pre-cues preceded the presence of a target. Subjects responded (with a key press) to the location of the target (right versus left of fixation). The cues could be valid (i.e., appear where the target would appear) or invalid (appear contralateral to where the target would appear). DNA sequencing assays were performed on buccal cells to genotype known genetic markers and these were examined for association with task scores. Here we show significant associations between visual orienting and genetic markers (on COMT, DAT1, and APOE; R²s from 4% to 9%).

Conclusions/Significance

One measure in particular – the response time cost of a single dim, invalid cue – was associated with dopaminergic markers on COMT and DAT1. Additionally, variations of APOE genotypes based on the ε2/ε3/ε4 alleles were also associated with response time differences produced by simultaneous cues with unequal luminances. We conclude that individual differences in visual orienting are related to several dopaminergic markers as well as to a cholinergic marker. These results challenge the view that orienting is not associated with genotypic variation in dopaminergic genes.     

Oral health status in elders from South Brazil: a population-based study

doi: 10.1111/j.1741‐2358.2011.00617.x Oral health status in elders from South Brazil: a population‐based study Objective: To assess the oral health status of community‐dwelling adults aged 60 years and older from southern Brazil and to determine demographics, socioeconomic, behavioural and dental risk indicators. Materials and methods: This cross‐sectional study used a multistage, probability sampling method to draw a representative sample of the metropolitan area of Porto Alegre, Brazil. A subsample of 217 subjects was included in this analysis. Oral mucosal lesions, dental caries, tooth loss and periodontal status (full‐mouth, six sites per tooth exam) were assessed by calibrated examiners. Results: Prevalence of edentulism was 39.5%, and mean tooth loss was 20.2 (SE = 0.6). Older individuals [Odds Ratio (OR) = 2.2], women (OR = 2.3), white people (OR = 5.9), individuals of lower socioeconomic status (OR = 5.6) and smokers (OR = 3.5) had higher likelihood of being edentulous. Approximately 36% of dentate individuals had caries and/or restoration affecting, in average, 5.0 teeth. Periodontitis affected 79% of subjects, and it was associated with older age (OR = 4.0), men (OR = 3.4) and large amounts of supragingival plaque (OR = 3.0). Conclusion: Poor oral health was observed in this elderly population from South Brazil. Sociodemographic disparities accounted for most of the burden of disease and treatment needs.     

Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study

Background

Although anxiety and depression have been classified as distinct traits of affective disorders, previous studies have reported their co-occurrence in subjects with migraine. However, few reports are available on the clinical implications of this comorbidity. This study is to assess the comorbidity of anxiety and depression in subjects with migraine and its clinical implications in a population-based sample from Korea.

Methods

We selected Korean subjects aged 19–69 years by the stratified random sampling method, and evaluated them using a semi-structured interview, designed to identify headache type, anxiety, and depression. We used Goldberg Anxiety Scale questions and Patient Health Questionnnaire-9 for the diagnosis of anxiety and depression, respectively.

Results

Of the 2,762 participants who completed the interview, 147 subjects (5.4%) were classified as having a migraine during the previous year. Among these 147 subjects, 17 (11.6%) had anxiety and depression, 28 (19.0%) had anxiety alone, 9 (6.1%) had depression alone, and 93 (63.3%) had neither anxiety nor depression. Headache frequency per month was remarkably higher in subjects having migraine with anxiety and depression (median [25–75 percentile values], 8.0 [2.5–21.0]) than in those having migraine with anxiety alone (2.0 [1.0–5.0], p?=?0.003), migraine with depression alone (1.0 [0.3–4.0], p?=?0.001), and migraine without anxiety or depression (1.0 [0.3–3.0], p?<?0.001). The migraine with anxiety alone (7.0 [6.0–8.0], p?=?0.011) group and migraine with anxiety and depression (7.0 [5.0–9.0], p?=?0.018) group showed higher Visual Analogue Scale scores for pain intensity compare to migraine without anxiety or depression (6.0 [5.0-7.0]) group.

Conclusions

Approximately 1/3 of migraineurs with anxiety had depression and 2/3 of migraineurs with depression had anxiety. Combination of anxiety and depression was associated with an increased headache frequency. Anxiety was associated with exacerbation of headache intensity.

     

Telomere length inversely correlates with radiosensitivity in human carcinoma cells with the same tissue background

A relationship between telomeres and radiosensitivity has been established by several studies based on non-mammalian model systems, mouse models, and few human genetic diseases. However, the relationship has not been proven in human carcinoma cells, which have more clinical significance than these other models. The present study aims to determine whether telomere length is related to radiosensitivity in human carcinoma cells, and to examine the influence of tissue or genetic background. Two HEp-2 larynx squamous carcinoma cell lines, eight hepatocellular carcinoma cell lines, and five breast cancer cell lines were used. Telomere length was determined by terminal restriction fragment (TRF) Southern blot analysis and cell survival was measured by a colony-forming assay. Our results indicated that there was a significant negative correlation of telomere length and radiosensitivity in the same tissue-derived cell lines, with or without the same genetic background. Thus, telomere length may be used as a promising tool to predict the radiosensitivity of human carcinomas.     

Long-term mortality of patients with septic ocular or central nervous system complications from pyogenic liver abscess: a population-based study

Background

Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period.

Methodology/Principal Findings

We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1% of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age <65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8% vs. 27.5%, p = 0.502). However, among patients <65 years old and a Charlson index ≤1, the 2-year mortality was significantly higher in those with than without complications (18.6% vs. 11.8%, p = 0.001).

Conclusions/Significance

Physicians should recognize that catastrophic disability due to ocular or neurological complications from PLA could lead to a poor long-term prognosis, and should follow-up these patients more closely.     

Decreased glomerular filtration rate is associated with mortality and cardiovascular events in patients with hypertension: a prospective study

Background

Few studies reported the associations between decreased glomerular filtration rate (GFR) and mortality, coronary heart disease (CHD), and stroke in hypertensive patients. We aim to assess the associations between GFR and mortality, CHD, and stroke in hypertensive patients and to evaluate whether low GFR can improve the prediction of these outcomes in addition to conventional cardiovascular risk factors.

Methods and Findings

This is an observational prospective study and 3,711 eligible hypertensive patients aged ≥5 years from rural areas of China were used for the present analysis. The associations between eGFR and outcomes, followed by a median of 4.9 years, were evaluated using Cox proportional hazards models adjusting for other potential confounders. Low eGFR was independently associated with risk of all-cause mortality, cardiovascular mortality, and incident stroke [multivariable adjusted hazard ratios (95% confidence intervals) for eGFR <60 ml/min/1.73 m² relative to eGFR ≥90 ml/min/1.73 m² were 1.824 (1.047–3.365), 2.371 (1.109–5.068), and 2.493 (1.193–5.212), respectively]. We found no independent association between eGFR and the risk of CHD. For 4-year all-cause and cardiovascular mortality, integrated discrimination improvement (IDI) was positive when eGFR were added to traditional risk factors (1.51%, P = 0.016, and 1.99%, P = 0.017, respectively). For stroke and CHD events, net reclassification improvements (NRI) were 5.9% (P = 0.012) and 1.8% (P = 0.083) for eGFR, respectively.

Conclusions

We have established an inversely independent association between eGFR and all-cause mortality, cardiovascular mortality, and stroke in hypertensive patients in rural areas of China. Further, addition of eGFR significantly improved the prediction of 4-year mortality and stroke over and above that of conventional risk factors. We recommend that eGFR be incorporated into prognostic assessment for patients with hypertension in rural areas of China.

Limitations

We did not have sufficient information on atrial fibrillation to control for the potential covariate. These associations should be further confirmed in future.     

Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

Introduction

Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.

Methods

Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.

Results

Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.

Conclusions

In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.     

Telomere length is independently associated with age,oxidative biomarkers,and sport training in skeletal muscle of healthy adult males

In skeletal muscle, which mainly contains postmitotic myonuclei, it has been suggested that telomere length remains roughly constant throughout adult life, or shortens in response to physiopathological conditions in muscle diseases or in the elderly. However, telomere length results from both the replicative history of a specific tissue and the exposure to environmental, DNA damage-related factors, therefore the predictive biological significance of telomere measures should combine the analysis of the various interactive factors. In the present study, we analysed any relationship between telomere length [mean and minimum terminal restriction fragment (TRF) length] chronological age, oxidative damage (4-HNE, protein carbonyls), catalase activity, and heat shock proteins expression (αB-crystallin, Hsp27, Hsp90) in semitendinous muscle biopsies of 26 healthy adult males between 20 and 50 years of age, also exploring the influence of regular exercise participation. The multiple linear regression analysis identified age, 4-HNE, catalase, and training status as significant independent variables associated with telomere length and jointly accounting for ～30–36% of interindividual variation in mean and/or minimum TRF length. No association has been identified between telomere length and protein carbonyl, αB-crystallin, Hsp27, and Hsp90, as well as between age and the variables related to stress response. Our results showed that skeletal muscle from healthy adults displays an age-dependent telomere attrition and that oxidised environment plays an age-independent contribution, partially influenced by exercise training.     

Expression of mutant or cytosolic PrP in transgenic mice and cells is not associated with endoplasmic reticulum stress or proteasome dysfunction

The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known. Several mutant PrPs misfold in the early secretory pathway and reside longer in the endoplasmic reticulum (ER) possibly stimulating ER stress-related pathogenic mechanisms. To investigate whether mutant PrP induced maladaptive responses, we checked key elements of the unfolded protein response (UPR) in transgenic mice, primary neurons and transfected cells expressing two different mutant PrPs. Because ER stress favors the formation of untranslocated PrP that might aggregate in the cytosol and impair proteasome function, we also measured the activity of the ubiquitin proteasome system (UPS). Molecular, biochemical and immunohistochemical analyses found no increase in the expression of UPR-regulated genes, such as Grp78/Bip, CHOP/GADD153, or ER stress-dependent splicing of the mRNA encoding the X-box-binding protein 1. No alterations in UPS activity were detected in mutant mouse brains and primary neurons using the Ub(G76V)-GFP reporter and a new fluorogenic peptide for monitoring proteasomal proteolytic activity in vivo. Finally, there was no loss of proteasome function in neurons in which endogenous PrP was forced to accumulate in the cytosol by inhibiting cotranslational translocation. These results indicate that neither ER stress, nor perturbation of proteasome activity plays a major pathogenic role in prion diseases.     

Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study

Background

The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP).

Methods and Findings

This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-α, IL-1β and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-α, CRP and IL-1β were 355 µmol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 µmol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-α and CRP and negatively with IL-1β (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P<0.05). In multivariable analyses, SUA was associated positively with CRP (β coefficient ± SE = 0.35±0.02, P<0.001), TNF-α (0.08±0.02, P<0.001) and IL-6 (0.10±0.03, P<0.001), and negatively with IL-1β (−0.07±0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated.

Conclusions

SUA was associated positively with IL-6, CRP and TNF-α and negatively with IL-1β, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation.