Lester Arguelles

Gene-vitamin D interactions on food sensitization: a prospective birth cohort study

To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H‐J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. Gene–vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442–1448.

A twin study of posttraumatic stress disorder symptoms and chronic widespread pain

Abstract Previous studies of the association between posttraumatic stress disorder (PTSD) and chronic widespread pain (CWP) or fibromyalgia have not examined the role of familial or genetic factors. The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community‐based sample of twin pairs, and if so, to ascertain if the association is due to familial or genetic factors. Data were obtained from the University of Washington Twin Registry, which contains 1042 monozygotic and 828 dizygotic twin pairs. To assess the symptoms of PTSD, we used questions from the Impact of Events Scale (IES). IES scores were partitioned into terciles. CWP was defined as pain located in 3 body regions lasting at least 1 week during the past 3 months. Random‐effects regression models, adjusted for demographic features and depression, examined the relationship between IES and CWP. IES scores were strongly associated with CWP (P < 0.0001). Compared to those in the lowest IES tercile, twins in the highest tercile were 3.5 times more likely to report CWP. Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins, this difference was not significant. Our findings suggest that PTSD symptoms, as measured by IES, are strongly linked to CWP, but this association is not explained by a common familial or genetic vulnerability to both conditions. Future research is needed to understand the temporal association of PTSD and CWP, as well as the physiological underpinnings of this relationship.

Gene polymorphisms, breast-feeding, and development of food sensitization in early childhood

BACKGROUND The effect of breast-feeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes. OBJECTIVE We sought to evaluate the effect of breast-feeding and gene-breast-feeding interactions on food sensitization (FS) in a prospective US birth cohort. METHODS This study included 970 children who were prospectively followed since birth. Breast-feeding history was obtained from a standardized questionnaire interview. FS was defined as a specific IgE level of 0.35 kU(A)/L or greater to any of 8 common food allergens. Eighty-eight potentially functional single nucleotide polymorphisms (SNPs) were genotyped from 18 genes involved in innate immunity or T(H)1/T(H)2 balance. Logistic regression models were used to test the effects of breast-feeding and gene-breast-feeding interactions on FS, with adjustment for pertinent covariates. RESULTS Children who were ever breast-fed (n = 739), including exclusively breast-fed children, were at a 1.5 (95% CI, 1.1-2.1; P = .019) times higher risk of FS than never breast-fed children (n = 231). This association was significantly modified by rs425648 in the IL-12 receptor β1 gene (IL12RB1; P for interaction = .0007): breast-feeding increased the risk of FS (odds ratio, 2.0; 95% CI, 1.4-3.1; P = .0005) in children carrying the GG genotype but decreased the risk (odds ratio, 0.6; 95% CI, 0.3-1.4; P = .252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the Toll-like receptor 9 (TLR9; rs352140) and thymic stromal lymphopoietin (TSLP; rs3806933) genes. The interaction between the combined genotypes of the 3 SNPs and breast-feeding on FS was even stronger (P for interaction < 10⁻⁵). CONCLUSION Our data suggest that the effect of breast-feeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.

Heritability and Environmental Factors Affecting Vitamin D Status in Rural Chinese Adolescent Twins

CONTEXT Factors associated with the high prevalence of vitamin D deficiency in China are not well described, especially among Chinese adolescents. OBJECTIVES The aim of the study was to examine important environmental or sociodemographic factors influencing 25-hydroxyvitamin D [25(OH)D] levels and estimate its heritability. DESIGN A sample of 226 male and female adolescent twins aged 13-20 yr from a large prospective twin cohort of rural Chinese children and adolescents that has been followed for 6 yr were evaluated. MAIN OUTCOME MEASURE(S) Blood level of 25(OH)D was measured using tandem mass spectrometry methodology. RESULTS The overall mean (SD) 25(OH)D level was 18.0 (9.4) ng/ml, with wide variation by gender and season. In males (47.4% of subjects), the mean (SD) 25(OH)D level was 12.1 (4.2) ng/ml in non-summer and 27.4 (8.8) ng/ml in summer; in females, it was 10.1 (4.1) ng/ml in non-summer and 19.5 (6.3) ng/ml in summer. A multivariate model that included gender, age, season, physical activity, and student status demonstrated that male gender, summer season, and high physical activity significantly increased 25(OH)D levels. Summer season and male gender also significantly decreased the risk of being in the lowest 25(OH)D tertile. Overall, 68.9% of the variability in 25(OH)D level was attributable to additive genetic influence. Stratification by gender found that in males, 85.9% of the variability in 25(OH)D level was attributable to such influence, but in females, it was only 17%. CONCLUSION In this sample of rural Chinese adolescents, 25(OH)D level was influenced by gender, season, and physical activity level. There was a strong genetic influence on 25(OH)D level in males only.

Vitamin D Deficiency in Children With Chronic Kidney Disease: Uncovering an Epidemic

BACKGROUND. Vitamin D deficiency in children adversely affects bone development by reducing mineralization. Children with chronic kidney disease are at risk for altered bone development from renal osteodystrophy and concomitant vitamin D deficiency. The pediatric Kidney Disease Outcomes Quality Initiative guidelines suggest measuring serum 25-hydroxyvitamin D (25[OH]D) levels if serum parathyroid hormone levels are above the target range for chronic kidney disease stages 2 and beyond, but the magnitude of vitamin D deficiency in children with chronic kidney disease is not well studied. OBJECTIVES. The purpose of this work was to determine whether children with chronic kidney disease had vitamin D deficiency, to evaluate whether the prevalence of vitamin D deficiency changed over time, and to examine seasonal and ethnic differences in 25(OH)D levels. METHODS. 25(OH)D levels in children with chronic kidney disease (stages 1–5) were measured over a 10-year period from 1987 to 1996. Data were also collected for a contemporary group of patients from 2005 to 2006. RESULTS. The prevalence of vitamin D deficiency ranged from 20% to 75% in the decade studied. There was a significant trend for decreasing 25(OH)D levels over the decade, both at the group and individual levels. Seasonal variation was noted. In our contemporary population with chronic kidney disease, the mean 25(OH)D level was 21.8 ng/mL; we found a prevalence of vitamin D deficiency of 39%. Black and Hispanic patients had lower levels of 25(OH)D than white patients. CONCLUSIONS. Children with chronic kidney disease have great risk for vitamin D deficiency, and its prevalence was increasing yearly in the studied decade. Contemporary data show that vitamin D deficiency remains a problem in these children. Sunlight exposure and ethnicity play a role in levels of 25(OH)D. Our data support the recent pediatric Kidney Disease Outcomes Quality Initiative guidelines for measurement of 25(OH)D levels in children with chronic kidney disease and secondary hyperparathyroidism.

Sleep, school performance, and a school-based intervention among school-aged children: a sleep series study in China.

Background Sufficient sleep during childhood is essential to ensure a transition into a healthy adulthood. However, chronic sleep loss continues to increase worldwide. In this context, it is imperative to make sleep a high-priority and take action to promote sleep health among children. The present series of studies aimed to shed light on sleep patterns, on the longitudinal association of sleep with school performance, and on practical intervention strategy for Chinese school-aged children. Methods and Findings A serial sleep researches, including a national cross-sectional survey, a prospective cohort study, and a school-based sleep intervention, were conducted in China from November 2005 through December 2009. The national cross-sectional survey was conducted in 8 cities and a random sample of 20,778 children aged 9.0±1.61 years participated in the survey. The five-year prospective cohort study included 612 children aged 6.8±0.31 years. The comparative cross-sectional study (baseline: n = 525, aged 10.80±0.41; post-intervention follow-up: n = 553, aged 10.81±0.33) was undertaken in 6 primary schools in Shanghai. A battery of parent and teacher reported questionnaires were used to collect information on children’s sleep behaviors, school performance, and sociodemographic characteristics. The mean sleep duration was 9.35±0.77 hours. The prevalence of daytime sleepiness was 64.4% (sometimes: 37.50%; frequently: 26.94%). Daytime sleepiness was significantly associated with impaired attention, learning motivation, and particularly, academic achievement. By contrast, short sleep duration only related to impaired academic achievement. After delaying school start time 30 minutes and 60 minutes, respectively, sleep duration correspondingly increased by 15.6 minutes and 22.8 minutes, respectively. Moreover, intervention significantly improved the sleep duration and daytime sleepiness. Conclusions Insufficient sleep and daytime sleepiness commonly existed and positively associated with the impairment of school performance, especially academic achievement, among Chinese school-aged children. The effectiveness of delaying school staring time emphasized the benefits of optimal school schedule regulation to children’s sleep health.

Does Genetic Regulation of IgE Begin In-Utero? Evidence from TH1/TH2 Gene Polymorphisms and Cord Blood Total IgE

BACKGROUND Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allergies and atopic dermatitis. Cord blood IgE (CBIgE) is a recognized risk factor for the subsequent development of allergic diseases. In contrast with numerous genetic studies of total serum IgE in children and adults, limited genetic studies on CBIgE have been conducted. OBJECTIVE To test the associations between functional or tagging single nucleotide polymorphisms (SNPs) in genes involved in the T(H)1/T(H)2 pathway and CBIgE in a large US inner-city birth cohort. METHODS CBIgE, measured by Phadia ImmnunoCAP, was analyzed as a continuous and a binary variable. The association of each SNP with the 2 outcomes was tested using tobit and logistic regression models, respectively, with adjustment for pertinent covariates, ancestral proportion, and multiple testing. Ethnic heterogeneity and gene-gene interactions were also explored. RESULTS Three SNPs (rs1800925, rs2069743, and rs1295686) in the IL13 gene were significantly associated with CBIgE concentration (P ≤ 6 × 10(-4), FDR-corrected P < .05). These SNPs jointly influenced CBIgE in a dose-response manner (P for trend = 9 × 10(-8)). Significant associations also were observed for SNPs in the IL-13 receptor α1 (rs5956080) and signal transducer and activator of transcription 6 (rs11172106) genes. Ethnicity-specific genetic effects were observed for SNPs in the IL5 and GATA3 genes. Several gene-gene interactions (including IL13-IL4 receptor and IL13-signal transducer and activator of transcription 6 interactions) were detected in relation to CBIgE. CONCLUSION Our data demonstrated that multiple SNPs were individually and jointly associated with CBIgE, with evidence of gene-gene interactions and ethnic heterogeneity. These findings suggest that genetic regulation of IgE may begin in utero.

Persistence and change of PTSD symptomatology: A longitudinal co-twin control analysis of the Vietnam Era Twin Registry

Abstract.Introduction:Previous twin studies have demonstrated a strong association between the degree of combat exposure and PTSD, and the continued presence of PTSD, almost two decades after combat. Independent genetic effects have also been demonstrated for both combat exposure and PTSD vulnerability in Vietnam veterans. The current study, involving a subset of male-male twin pairs discordant for service in Southeast Asia (SEA), is a follow-up to an earlier study conducted in 1987. The purpose of this study is to examine the changes in the combat exposure-PTSD relationship over an additional decade of time.Methods:The Mississippi Scale for Combat-Related or Civilian PTSD was administered by telephone in 1997 during a follow-up survey of the Vietnam Era Twin Registry. Only twins discordant for service in Southeast Asia who originally participated in the 1987 study were included. Results of this scale and the original 1987 PTSD symptom scale were separately standardized using z-score transformations and used as dependent variables in a random effects regression model with zygosity, time and combat exposure as independent variables. Main effects and interactions were estimated to address whether there were differential effects of combat on PTSD over time, and whether there was evidence of genetic covariation between combat exposure and PTSD in 1987 that persisted to 1997.Results:Combat exposure was strongly associated with PTSD in both 1987 and 1997. Although still highly significant, the effect sharply diminished over time. There is little evidence for a shared genetic vulnerability between combat and PTSD in either 1987 or 1997.Conclusion:This analysis documents the continuing role of combat exposure (i. e., trauma severity) on the persistence and chronicity of PTSD. Nearly 25 years after the end of hostilities, PTSD symptoms continue to be elevated in those exposed to the highest levels of combat. There is no evidence that genetic influences on exposure to combat are shared with those inducing a genetic vulnerability to PTSD. Clinicians need to be aware of the persistent and long-term residual effects of trauma exposure

Short sleep duration is associated with insulin resistance independent of adiposity in Chinese adult twins

OBJECTIVE To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity. METHODS This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire were modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates. RESULTS In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (≤ 7 h/night) sleep duration was associated with a higher HOMA-IR (p=0.003) compared with normal sleep duration (>7 to ≤ 8 h/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF (p=0.026). Long sleep duration (> 8 h/night) was not significantly associated with HOMA-IR. CONCLUSION In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.

Longitudinal trajectory of vitamin D status from birth to early childhood in the development of food sensitization

Background:Increasing evidence supports the immunomodulatory effect of vitamin D on allergic diseases. The combined role of prenatal and postnatal vitamin D status in the development of food sensitization (FS) and food allergy remains understudied.Methods:Plasma 25-hydroxyvitamin D (25(OH)D) levels of 460 children in the Boston Birth Cohort (BBC) were measured at birth and early childhood, and the subjects were genotyped for rs2243250 (C-590T) in the IL4 gene. We defined FS as specific IgE levels of ≥0.35 kUA/l to any of eight common food allergens; we defined persistently low vitamin D status as cord blood 25(OH)D <11 ng/ml and postnatal 25(OH)D <30 ng/ml.Results:We observed a moderate correlation between cord blood 25(OH)D at birth and venous blood 25(OH)D measured at 2–3 y (r = 0.63), but a weak correlation at <1 y (r = 0.28). There was no association between low vitamin D status and FS at any single time point alone. However, in combination, persistence of low vitamin D status at birth and in early childhood increased the risk of FS (odds ratio (OR) = 2.03, 95% confidence interval (CI): 1.02–4.04), particularly among children carrying the C allele of rs2243250 (OR = 3.23, 95% CI: 1.37–7.60).Conclusion:Prenatal and early postnatal vitamin D levels, along with individual genetic susceptibility, should be considered in assessing the role of vitamin D in the development of FS and food allergy.