Ali H. Ziyab

Developmental trajectories of Body Mass Index from infancy to 18 years of age: prenatal determinants and health consequences

Background Knowledge on the long-term development of adiposity throughout childhood/adolescence and its prenatal determinants and health sequelae is lacking. We sought to (1) identify trajectories of Body Mass Index (BMI) from 1 to 18 years of age, (2) examine associations of maternal gestational smoking and early pregnancy overweight with offspring BMI trajectories and (3) determine whether BMI trajectories predict health outcomes: asthma, lung function parameters (forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio), and blood pressure, at 18 years. Methods The Isle of Wight birth cohort, a population-based sample of 1456 infants born between January 1989 and February 1990, was prospectively assessed at ages 1, 2, 4, 10 and 18 years. Group-based trajectory modelling was applied to test for the presence of latent BMI trajectories. Associations were assessed using log-binomial and linear regression models. Results Four trajectories of BMI were identified: ‘normal’, ‘early persistent obesity’, ‘delayed overweight’, and ‘early transient overweight’. Risk factors for being in the early persistent obesity trajectory included maternal smoking during pregnancy (RR 2.16, 95% CI 1.02 to 4.68) and early pregnancy overweight (3.16, 1.52 to 6.58). When comparing the early persistent obesity to the normal trajectory, a 2.15-fold (1.33 to 3.49) increased risk of asthma, 3.2% (0.4% to 6.0%) deficit in FEV1/FVC ratio, and elevated systolic 11.3 mm Hg (7.1 to 15.4) and diastolic 12.0 mm Hg (8.9 to 15.1) blood pressure were observed at age 18 years. Conclusions Maternal prenatal exposures show prolonged effects on offsprings propensity towards overweight-obesity. Distinct morbid BMI trajectories are evident during the first 18 years of life that are associated with higher risk of asthma, reduced FEV1/FVC ratio, and elevated blood pressure.

Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study

Background Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a net remission during childhood is assumed.

Epigenetic mechanisms and models in the origins of asthma.

Purpose of reviewEpigenetic mechanisms have the ability to alter the phenotype without changing the genetic code. The science of epigenetics has grown considerably in recent years, and future epigenetically based treatments or prevention strategies are likely. Epigenetic associations with asthma have received growing interest because genetic and environmental factors have been unable to independently explain the cause of asthma. Recent findingsRecent findings suggest that both the environment and underlying genetic sequence variation influence DNA methylation, which in turn seems to modify the risk conferred by genetic variants for various asthma phenotypes. In particular, DNA methylation may act as an archive of a variety of early developmental exposures, which then can modify the risk related to genetic variants. SummaryCurrent asthma treatments may control the symptoms of asthma but do not modify its natural history. Epigenetic mechanisms and novel explanatory models provide burgeoning approaches to significantly increase our understanding of the initiation and progression of asthma. Due to the inheritance of epigenetics, we anticipate a rapid emergence of critical information that will provide novel treatment strategies for asthma in the current generation and ultimately the prevention of asthma in future generations.

DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss-of-function variants

Background  Loss‐of‐function variants within the filaggrin gene (FLG) are associated with a dysfunctional skin barrier that contributes to the development of eczema. Epigenetic modifications, such as DNA methylation, are genetic regulatory mechanisms that modulate gene expression without changing the DNA sequence.

Epidemiologic Methods of Assessing Asthma and Wheezing Episodes in Longitudinal Studies: Measures of Change and Stability

Background In settings in which diseases wax and wane, there is a need to measure disease dynamics in longitudinal studies. Traditional measures of disease occurrence (eg, cumulative incidence) do not address change or stability or are limited to stable cohorts (eg, incidence) and may thus lead to erroneous conclusions. To illustrate how different measures can be used to detect disease dynamics, we investigated sex differences in the occurrence of asthma and wheezing, using a population-based study cohort that covered the first 18 years of life. Methods In the Isle of Wight birth cohort (n = 1456), prevalence, incidence, cumulative incidence, positive and negative transitions, and remission were determined at ages 1 or 2, 4, 10, and 18 years. Latent transition analysis was used to simultaneously identify classes of asthma and wheezing (related phenotypes) and characterize transition probabilities over time. Trajectory analysis was used to characterize the natural history of asthma and wheezing. Results Regarding time-specific changes, positive and negative transition probabilities were more informative than other measures of associations because they revealed a sex switchover in asthma prevalence (P < 0.05). Transition probabilities were able to identify the origin of a sex-specific dynamic; in particular, prior wheezing transitioned to asthma at age 18 years among girls but not among boys. In comparison with latent transition analysis, trajectory analysis did not directly identify a switchover in prevalence among boys and girls. Conclusions In longitudinal analyses, transition analyses that impose minimal restrictions on data are needed in order to produce appropriate information on disease dynamics.

Interplay of filaggrin loss-of-function variants, allergic sensitization, and eczema in a longitudinal study covering infancy to 18 years of age.

Background Immune specific genes as well as genes regulating the formation of skin barrier are major determinants for eczema manifestation. There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization. To investigate the time-order between eczema and allergic sensitization with respect to FLG variants, data from a large prospective study covering infancy to late adolescence were analyzed. Methodology/Principal Findings Repeated measurements of eczema and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10 to 18 years. FLG variants were genotyped in 1,150 participants. Over the three transition periods, in temporal sequence analyses of initially eczema-free participants, the combined effect of FLG variants and allergic sensitization showed a 2.92-fold (95% CI: 1.47–5.77) increased risk ratio (RR) of eczema in subsequent examinations. This overall risk was more pronounced at a younger age (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96–21.33). In contrast, FLG variants in combination with eczema showed a weaker, but significant, risk ratio for subsequent allergic sensitization only up to 10 years of age. Conclusions/Significance Taking the time order into account, this prospective study demonstrates for the first time, that a combination of FLG variants and allergic sensitization increased the risk of eczema in subsequent years. Also FLG variants interacted with eczema and increased the risk of subsequent allergic sensitization, which, was limited to the younger age. Hence, early restoration of defective skin barrier could prevent allergic sensitization and subsequently reduce the risk of eczema development.

Epigenomics and allergic disease.

Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

Allergic sensitization and filaggrin variants predispose to the comorbidity of eczema, asthma, and rhinitis: results from the Isle of Wight birth cohort

Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking.

Incidence and trend of road traffic injuries and related deaths in Kuwait: 2000-2009

Road traffic injuries (RTIs), disabilities and deaths are recognised as a major public health problem worldwide. This study aimed to quantify the magnitude and the trends of RTI-related fatal and non-fatal injuries in Kuwait for the period 2000-2009. Data on road traffic crashes and related events (i.e., fatal and non-fatal minor and severe injuries) were obtained from police records, and the population data were sought from Ministry of Interior, Kuwait. From 2000 to 2009, 11,591 non-fatal RTIs and 3891 RTIs-related deaths occurred in Kuwait. Non-fatal severe RTIs accounted for 28.2% of the total non-fatal RTIs. Of the 2945 RTI-related deaths that occurred from 2003 to 2009, majority were amongst males (87.3%) and in the age range of 20-59 years (70.8%). The mean (SD) annual mortality rates for the 10-year study period (2000-2009) were 14 (1) per 100,000 population and 36 (2) per 100,000 registered vehicles. From 2000 to 2009, population-based and registered vehicle-based overall RTI-related crude mortality rates decreased by 20% and 29%, respectively. However, Poisson regression analyses showed that the overall slightly decreasing trends were statistically non-significant both for population-based crude mortality rate (trend coefficient=-0.016; p(trend)=0.587) and registered vehicle-based crude mortality rate (trend coefficient=-0.024; p(trend)=0.192). Furthermore, the trend in population-based age-adjusted RTI-related mortality rate for 2003-2009 was also statistically non-significant (trend coefficient=-0.050; p(trend)=0.284). For non-fatal severe RTIs, the overall mean (SD) annual rates per 100,000 population and 100,000 registered vehicles were 44 (23) and 113 (60) with corresponding total reduction of 61% and 66% from 2000 to 2009. The overall declining trends in minor and severe RTI rates (both population based and registered vehicles based) were statistically significant (p(trend)<0.001). Despite declined minor and severe RTI rates, the RTI-related crude and age-adjusted mortality rates during the past decade continued to be high for a high-income country. Targeted interventions may help reduce the burden of minor and severe RTIs and related deaths in Kuwait and other countries in the region.

Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study

BackgroundEczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk.MethodsData from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema.ResultsUnder a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted Pinteraction = 0.046; PAPA: Pinteraction = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 – 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 – 3.12; P = 0.002) in the PAPA study population.ConclusionsOur study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis).