Evidence regarding the role of long-term exposure to ultrafine particles (<0.1 μm, UFP) in asthma onset is scarce.
We examined the association between exposure to UFP and asthma development in the ...Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and assessed whether there is an association with UFP, independent of other air pollutants.
Data from birth up to age 20 years from 3687 participants were included. Annual average exposure to UFP at the residential addresses was estimated with a land-use regression model. Overall and age-specific associations of exposure at the birth address and current address at the time of follow-up with asthma incidence were assessed using discrete-time hazard models adjusting for potential confounders. We investigated both single- and two-pollutant models accounting for co-exposure to other air pollutants (PM2.5 and PM10 mass concentrations, nitrogen dioxide, and PM2.5 absorbance).
A total of 812 incident asthma cases were identified. Overall, we found that higher UFP exposure was associated with higher asthma incidence (adjusted odds ratio (95% confidence interval) 1.08 (1.02,1.14) and 1.06 (1.00, 1.12) per interquartile range increase in exposure at the birth address and current address at the time of follow-up, respectively). Age-specific associations were not consistent. The association was no longer significant after adjustment for other traffic-related pollutants (nitrogen dioxide and PM2.5 absorbance).
Our findings support the importance of traffic-related air pollutants for asthma development through childhood and adolescence, but provide little support for an independent effect of UFP.
•Studies on long-term ultrafine particle (UFP) exposure and asthma onset are scarce.•We assessed associations of UFP exposure and asthma onset until age 20.•We found that higher UFP exposure was associated with higher asthma incidence.•Associations did not persist after adjustment for other traffic-related pollutants.
Objectives: To assess the contribution of out-of-home (OH) energy and nutrient intake to total dietary intake, and to compare out- versus in-home nutrient patterns among 27 centres in 10 countries ...participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 participants aged between 35–74 years completed a standardized 24-h dietary recall using a software programme (EPIC-Soft) that recorded the place of food/drink consumption. Eating OH was defined as the consumption of foods and beverages anywhere other than in household premises, irrespective of the place of purchase/preparation. Nutrient intakes were estimated using a standardized nutrient database. Mean intakes were adjusted for age and weighted by season and day of recall. Results: Among women, OH eating contributed more to total fat intake than to intakes of protein and carbohydrates. Among both genders, and particularly in southern Europe, OH eating contributed more to sugar and starch intakes and less to total fibre intake. The contribution of OH eating was also lower for calcium and vitamin C intakes. The composition of diet at home was different from that consumed out of home in southern countries, but was relatively similar in the north. Conclusions: In northern Europe, OH and in-home eating are homogeneous, whereas southern Europeans consider OH eating as a distinctive occasion. In most centres, women selected more fat-rich items when eating out.
Heritability estimates of MetS range from approximately 10%–30%. The genetic variation that is shared among MetS features can be calculated by genetic correlation coefficients. The objective of this ...paper is to identify MetS feature as well as MetS related features which have much genetic variation in common, by reviewing the literature regarding genetic correlation coefficients. Identification of features, that have much genetic variation in common, may eventually facilitate the search for pleitropic genetic variants that may explain the clustering of MetS features.
A PubMed search with the search terms “(metabolic syndrome OR insulin resistance syndrome) and (heritability OR genetic correlation OR pleiotropy)” was performed. Studies published before 7th July 2011, which presented genetic correlation coefficients between the different MetS features and genetic correlation coefficients of MetS and its features with adipose tissue-, pro-inflammatory and pro-thrombotic biomarkers were included.
Nine twin and 19 family studies were included in the review. Genetic correlations varied, but were strongest between waist circumference and HOMA-IR (r2: 0.36 to 0.79, median: 0.50), HDL cholesterol and triglycerides (r2: −0.05 to −0.59, median −0.45), adiponectin and MetS (r2: −0.32 to −0.43; median −0.38), adiponectin and insulin (r2: −0.10 to −0.60; median −0.30) and between adiponectin and HDL-cholesterol (r2: −0.22 to −0.51, median −0.29).
In conclusion, heritability studies suggest that genetic pleiotropy exist especially between certain MetS features, as well as between MetS and adiponectin. Further research on actual genetic variants responsible for the genetic pleiotropy of these combinations will provide more insight into the etiology of MetS.
► Strongly genetically correlated features share much genetic variation. ► We reviewed studies on genetic correlations of metabolic syndrome features. ► Waist circumference and HOMA-IR were strongly genetically correlated. ► HDL cholesterol and triglycerides were strongly genetically correlated. ► Adiponectin was clearly genetically correlated with metabolic syndrome.
Background: As nuclear receptors and transcription factors have an important regulatory function in adipocyte differentiation and fat storage, genetic variation in these key regulators and downstream ...pathways may be involved in the onset of obesity. Objective: To explore associations between single nucleotide polymorphisms (SNPs) in candidate genes from regulatory pathways that control fatty acid and glucose metabolism, and repeated measurements of body mass index (BMI) and waist circumference in a large Dutch study population. Methods: Data of 327 SNPs across 239 genes were analyzed for 3575 participants of the Doetinchem cohort, who were examined three times during 11 years, using the Illumina Golden Gate assay. Adjusted random coefficient models were used to analyze the relationship between SNPS and obesity phenotypes. False discovery rate q-values were calculated to account for multiple testing. Significance of the associations was defined as a q-value <or= 0.20. Results: Two SNPs (in NR1H4 and SMARCA2 in women only) were significantly associated with both BMI and waist circumference. In addition, two SNPs (in SIRT1 and SCAP in women only) were associated with BMI alone. A functional SNP, in IL6, was strongly associated with waist. Conclusion: In this explorative study among participants of a large population-based cohort, five SNPs, mainly located in transcription mediator genes, were strongly associated with obesity phenotypes. The results from whole genome and candidate gene studies support the potential role of NR1H4, SIRT1, SMARCA2 and IL6 in obesity. Although replication of our findings and further research on the functionality of these SNPs and underlying mechanism is necessary, our data indirectly suggest a role of GATA transcription factors in weight control.
Folate metabolism is thought to play an important role in carcinogenesis through its involvement in both DNA methylation and nucleotide synthesis. A common Ala(222)/Val variant in the ...methylenetetrahydrofolate reductase (MTHFR) gene leads to a disturbed folate metabolism and is associated with decreased genomic DNA methylation. We previously reported that the MTHFR Val/Val genotype was associated with increased cancer mortality in men from a population-based cohort of subjects ages > or = 85 years. To further explore the deleterious effects of the MTHFR genotype, we studied the association of the genotype with cancer risk in 860 men ages 65-84 years who were followed >10 years (Zutphen Elderly Study). During follow-up, 149 new cases of cancer occurred among the 793 men without cancer at baseline. The risk of developing cancer was 1.80-fold (95% confidence interval, 1.09-3.00) higher among men with the Val/Val genotype than among men with the Ala/Ala genotype. Except for lung cancer relative risk (RR), 1.15, the risks of common forms of cancers were significantly increased among men with the Val/Val genotype cancer of the prostate (RR, 3.48); the colorectum (RR, 3.65); the kidney and bladder (RR, 5.48). The risks of cancer were particularly increased among men with a lower folate and a higher alcohol intake and men of an older age. In conclusion, our current and previous studies in two independent populations indicate that a common Ala/Val variant in the MTHFR gene is a risk factor for cancer in elderly men from the general population. The mechanism underlying this association might involve genomic instability as a result of insufficient methylation of genomic DNA.
Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies ...show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.
Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals -0.9%, 1.6%; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals 0.99, 1.04; P=0.20).
This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.
This study was designed to investigate the association(s) between heterogeneity at the cholesteryl ester transfer protein (CETP) gene locus, CETP plasma concentrations, and HDL cholesterol levels. ...Healthy men with the lowest, median, and highest deciles of HDL cholesterol were selected from a large population database. We accounted for factors that are known to influence HDL cholesterol levels, such as smoking, exercise, body mass index, alcohol consumption, and blood pressure. Plasma CETP concentrations were measured, and we determined the allele frequency distribution of six CETP DNA polymorphisms. The group with low HDL cholesterol exhibited a significant increase in CETP concentration compared with both the median and high HDL cholesterol groups, whereas CETP concentrations did not differ among the groups with median and high HDL cholesterol. The allele frequency distributions of the TaqIB (intron 1), Msp I (intron 8), and Rsa I (exon 14) polymorphisms differed significantly between the groups with low and high HDL cholesterol. Further analysis revealed that the Msp I polymorphism had a 1.5-fold larger impact on CETP concentration than the TaqIB polymorphism and a fivefold larger impact than the Rsa I polymorphism. In conclusion, we demonstrated that heterogeneity at the CETP gene locus is correlated with CETP plasma concentrations and HDL cholesterol levels. More specifically, our data indicate the presence of a strong association between common variants of the CETP gene, high plasma CETP concentrations, and consequently hypoalphalipoproteinemia in healthy white men.
We investigated HFE C282Y and H63D allele frequencies in three Dutch towns in the Netherlands, as well as their association with cardiovascular disease (CVD) mortality. Study subjects were selected ...from participants of the Monitoring Project on Cardiovascular Disease Risk Factors in the Netherlands carried out in Amsterdam, Doetinchem and Maastricht among > 35000 subjects, 20-59 years of age. Mortality follow-up lasted 9 to 13 years. A random sample of the cohort (n = 1075) provided information on the total study population. The random sample and all CVD deaths (n = 301) were genotyped for the C282Y and H63D mutation. Adjusted hazard ratios (HR) for CVD mortality were calculated per genotype.
C282Y allele frequencies differed significantly between the towns investigated (p = 0.017), whereas the allele frequencies of H63D were similar (p = 0.141) across towns. In Maastricht we found a C282Y allele frequency of 0.086 compared to 0.055 in Amsterdam and 0.054 in Doetinchem. C282Y and H63D heterozygosity did not predict fatal CVD in either men or women, whereas homozygosity for the H63D mutation increased fatal CVD in women (adjusted HR = 8.5; 95% CI = 2.3-31.1). The unexpected high C282Y allele frequency in Maastricht is in line with the recent evidence of a Celtic origin of citizens from the former southern Netherlands and with prehistorical population migrations revealed in the context of the international Genographic Project, a landmark study of prehistorical human migrations around the globe. We recommend that when designing national screening programmes and national registries for genetic disorders, potential regional prevalence differences should be taken into account.
Recently, polymorphisms in thrombospondin (THBS) genes coding for THBS-1 (N700S), THBS-2 (T>G substitution in 3'-untranslated region), and THBS-4 (A387P) genes were proposed to modulate the risk of ...premature coronary artery disease (CAD) or myocardial infarction (MI). It was our objective to verify this hypothesis in an independent cohort.
We performed a case-control study among patients (n=503) referred to our institution for symptomatic CAD that occurred before the age of 50 years and a group of age- and sex-matched population-based controls free of CAD (n=1071). The THBS-1 variant allele was not associated with an altered risk of premature CAD or MI. Homozygosity for the THBS-2 variant allele and the THBS-4 variant (387P) allele was significantly associated with a reduced risk of premature MI compared with wild-type individuals (OR=0.44, 0.24 to 0.84 and OR=0.43, 0.22 to 0.85, respectively). The latter observation is in contrast with a previous report, although confidence intervals overlap.
We conclude that a relationship between the THBS-1 N700S polymorphism and premature CAD is unlikely. For the THBS-4 A387P polymorphism, additional studies are required to elucidate its role in premature CAD. Finally, we conclude that the THBS-2 polymorphism is associated with a reduced risk of premature MI.
To examine whether the association between abdominal obesity and hyperglycemia differs according to the presence of a parental history of diabetes.
We conducted a cross-sectional study of 3,068 men ...and women, aged 20-65 years, without known diabetes who were fasting participants of a population-based study in three Dutch towns. Hyperglycemia was defined as a fasting plasma glucose concentration of 6.1 mmol/l (American Diabetes Association criterion). Waist circumference was categorized according to previously defined waist action levels. All estimates were adjusted for age and town.
The regression coefficients for the association between waist circumference and fasting plasma glucose were larger in participants who had a parental history of diabetes than in those who did not (men beta = 0.31 vs. 0.16 mmol/SD, P for interaction = 0.003; women beta = 0.24 vs. 0.11 mmol/SD, P = 0.002). Furthermore, larger waist circumference (men > or = 94 vs. < 94 cm, women > or = 88 vs. < 80 cm) was associated with a greater excess prevalence of hyperglycemia in participants who had a parental history of diabetes than in those who did not (men 12.4 vs. 2.0%, P = 0.03; women 13.6 vs. 5.9%, P = 0.05). Adjustment for physical activity, alcohol intake, smoking, and educational level did not materially change the results.
These findings indicate that the association between abdominal obesity and hyperglycemia is stronger in the presence of a parental history of diabetes. Blood glucose screening may be warranted at lower levels of waist circumference in individuals with a parental history of diabetes.
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