PRKCA: A Positional Candidate Gene for Body Mass Index and Asthma
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC2771573 | biostudies-literature | 2009 Aug
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Asthma incidence and prevalence are higher in obese individuals. A potential mechanistic basis for this relationship is pleiotropy. We hypothesized that significant linkage and candidate-gene association would be found for body mass index (BMI) in a population ascertained on asthma affection status. Linkage analysis for BMI was performed on 657 subjects in eight Costa Rican families enrolled in a study of asthma. Family-based association studies were conducted for BMI with SNPs within a positional candidate gene, PRKCA. SNPs within PRKCA were also tested for association with asthma. Association studies were conducted in 415 Costa Rican parent-child trios and 493 trios participating in the Childhood Asthma Management Program (CAMP). Although only modest evidence of linkage for BMI was obtained for the whole cohort, significant linkage was noted for BMI in females on chromosome 17q (peak LOD = 3.39). Four SNPs in a candidate gene in this region (PRKCA) had unadjusted association p values < 0.05 for BMI in both cohorts, with the joint p value for two SNPs remaining significant after adjustment for multiple comparisons (rs228883 and rs1005651, joint p values = 9.5 x 10(-)(5) and 5.6 x 10(-)(5)). Similarly, eight SNPs had unadjusted association p values < 0.05 for asthma in both populations, with one SNP remaining significant after adjustment for multiple comparisons (rs11079657, joint p value = 2.6 x 10(-)(5)). PRKCA is a pleiotropic locus that is associated with both BMI and asthma and that has been identified via linkage analysis of BMI in a population ascertained on asthma.
| S-EPMC2706964 | biostudies-literature
Project description:Several studies have found an association between overweight and asthma, yet the temporal relationship between their onsets remains unclear. We investigated the development of body mass index (BMI) from birth to adolescence among 2,818 children with and without asthma from a Swedish birth cohort study, the BAMSE (a Swedish acronym for "children, allergy, milieu, Stockholm, epidemiology") Project, during 1994-2013. Measured weight and height were available at 13 time points throughout childhood. Asthma phenotypes (transient, persistent, and late-onset) were defined by timing of onset and remission. Quantile regression was used to analyze percentiles of BMI, and generalized estimating equations were used to analyze the association between asthma phenotypes and the risk of high BMI. Among females, BMI development differed between children with and without asthma, with the highest BMI being seen among females with persistent asthma. The difference existed throughout childhood but increased with age. For example, females with persistent asthma had 2.33 times' (95% confidence interval: 1.21, 4.49) greater odds of having a BMI above the 85th percentile at age ≥15 years than females without asthma. Among males, no clear associations between asthma and BMI were observed. In this study, persistent asthma was associated with high BMI throughout childhood among females, whereas no consistent association was observed among males.
| S-EPMC5860555 | biostudies-literature
Project description:Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.
| S-EPMC8531156 | biostudies-literature
Project description:BackgroundThe relationship between obesity and asthma is an area of debate.ObjectiveTo investigate the association of elevated body mass index (BMI) at a young age and young adult asthma.MethodsBMI, questionnaires, and serologic tests results were analyzed in participants of a predominantly white, middle-class, population-based birth cohort from Detroit, Michigan at 6 to 8 and 18 years of age. Asthma diagnosis was based on medical record data. Allergen specific IgE was analyzed using UniCAP, with atopy defined as 1 or more allergen specific IgE levels of 0.35 kU/L or higher. Overweight was defined as a BMI in 85th percentile or higher.ResultsA total of 10.6% of overweight males at 6 to 8 years of age had current asthma at 18 to 20 years of age compared with 3.2% of males who were normal or underweight (relative risk [RR], 3.3; 95% confidence interval [CI], 1.0-11.0; P=.048). A total of 19.6% of females who were overweight at 6 to 8 years of age had asthma compared with 10.3% of females who were normal or underweight (RR, 1.9; 95% CI, 0.9-3.9; P=.09). After adjustment for atopy at 6 to 8 years of age, overweight males had an adjusted RR of 4.7 (95% CI, 1.4-16.2; P=.01), and overweight females had an adjusted RR of 1.7 (95% CI, 0.8-3.3; P=.15). Change in BMI between 6 to 8 years of age and 18 to 20 years of age was also examined. Patients with persistently elevated BMI exhibited increased risk of asthma as young adults (RR, 2.4; 95% CI, 1.2-4.7) but not with an increasing BMI (RR, 0.8; 95% CI, 0.3-2.2) or a decreasing BMI (RR, 0.8; 95% CI, 0.3-2.2).ConclusionOverweight males 6 to 8 years of age have increased risk of asthma as young adults. Being overweight remains a predictor of asthma after adjustment for early atopy. A similar but not statistically significant trend was also seen among overweight females. Overweight body habitus throughout childhood is a risk factor for young adult asthma.
| S-EPMC3769639 | biostudies-literature
Project description:To examine the association between body mass index (BMI) percentile and asthma in children 2-11 years of age, we performed a cross-sectional analysis of 853 Black and Hispanic children from a community-based sample of 2- to 11-year olds with measured heights and weights screened for asthma by the Harlem Children's Zone Asthma Initiative. Current asthma was defined as parent/guardian-reported diagnosis of asthma and asthma-related symptoms or emergency care in the previous 12 months. Among girls, asthma prevalence increased approximately linearly with increasing body mass index (BMI) percentile, from a low of 12.0% among underweight girls (BMI </=5th percentile) to a high of 33.3% among girls at risk for overweight (BMI 85th-94th percentile). Among boys, asthma prevalence was associated in a U-shaped curve with the extremes of BMI percentile, that is, 36.4% among underweight boys, 19.1% among normal weight boys (BMI 6th-84th percentile), and 34.8% among overweight boys (>95th percentile). After adjusting for age, race/ethnicity, and household smoking, among girls, having asthma was associated with being at risk for overweight (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-5.0) and being overweight (OR, 2.1; 95% CI, 1.2-3.8) compared to normal weight; among boys, having asthma was associated both with overweight (OR, 2.4; 95% CI, 1.4-4.3) and with underweight (OR, 2.9; 95% CI, 1.1-7.7). Large, prospective studies that include very young children are needed to further explore the observed association between underweight and asthma among boys. Early interventions that concomitantly address asthma and weight gain are needed among pre-school and school-aged children.
| S-EPMC2527185 | biostudies-other
Project description:BackgroundSparse data are available on the relationship between prenatal exposures and asthma during later childhood. In a longitudinal study of adolescents and their mothers, we examined the association of (i) maternal prepregnancy body mass index (BMI) and (ii) gestational weight gain (GWG), with incidence of allergic and nonallergic asthma in offspring.MethodsAnalyses were conducted using data from 12 963 children aged 9-14 years at enrolment in the Growing Up Today Study, and their mothers, who are participants in the Nurses' Health Study II. Physician-diagnosed asthma and allergies were assessed by questionnaires sent regularly to participants and their mothers. Logistic regression was used to evaluate associations of maternal BMI and GWG with offspring asthma, overall and by subtype.ResultsPhysician-diagnosed asthma during childhood or adolescence was reported by 2694 children (21%). Maternal prepregnancy overweight (OR: 1.19, 95% CI: 1.03-1.38) and obesity (1.34, 1.08-1.68) were associated with offspring asthma. In asthma subtype analyses, the association was seen only for asthma onset before age 12 years. Moreover, the association of maternal obesity with nonallergic asthma was observed in boys (2.39, 1.40-4.09) and not in girls (0.96, 0.50-1.85; Pinteraction = 0.03); the opposite pattern was suggested for allergic asthma. With regard to GWG, an association was suggested between gains of <15 lb and higher risk of offspring asthma (1.28, 0.98-1.66), without clear allergy- or sex-related patterns.ConclusionThe relation of several prenatal factors to risk of childhood asthma supports the early origins hypothesis for asthma. The observed allergy- and sex-specific patterns suggest multiple etiologic pathways.
| S-EPMC4975656 | biostudies-literature
Project description:Sputum neutrophils are associated with severe asthma, poor pulmonary function and high body mass index (BMI) in adult patients. However, little is known about the relationships between blood neutrophils, BMI and asthma severity in pediatric patients. This brief report is to assess the predictive value of blood neutrophils for asthma severity, BMI and pulmonary function in adolescents with asthma. The study included 166 adolescents with physician diagnosed asthma for at least 1 year. Participants were recruited from three metropolitan cities in the U.S. BMI-for-age percentile (BMI %) was determined by standardized charts and absolute neutrophil counts (cells/μL) were obtained from the complete blood count. Asthma severity was measured based on the national guidelines. Spirometry was performed to obtain percent predicted values for Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC ratio as markers for pulmonary function. The average age of participants was 14.79 years (± 1.86) and 54% were female. The majority (84%) were black. Fifty-five percent of the sample were either overweight (21%) or obese (34%). Blood neutrophil count was significantly correlated with BMI% (r=0.25, p=.001), but not with symptom severity (r=0.087, p=.268), FEV1 (r=-0.00, p=.937), or FVC (r=-0.010, p=.897).After controlling for sex, age, and age at asthma diagnosis, blood neutrophil count was a significant predictor for overweightness or obesity (OR=1.38, 95% CI 1.11, 1.75, p=0.01). Elevated blood neutrophils are associated with higher BMI, but not lung function or symptom severity in our adolescent sample with asthma. This study suggests blood neutrophils may be a potential inflammatory biomarker for overweightness and obesity in adolescents with asthma, but not for asthma morbidity.
| S-EPMC6287916 | biostudies-literature
Project description: Not available
| S-EPMC5708874 | biostudies-literature
Project description:BackgroundAlthough obesity has been hypothesized to worsen asthma, data from studies of subjects with well-characterized asthma are lacking.ObjectiveWe sought to evaluate the relationship between body mass index (BMI), asthma impairment, and response to therapy.MethodsBMI (in kilograms per meter squared) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies.ResultsOne thousand two hundred sixty-five subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean versus overweight/obese asthmatic subjects demonstrated small differences in FEV1 (3.05 vs 2.91 L, P = .001), FEV1/forced vital capacity ratio (mean, 83.5% vs 82.4%; P = .01), rescue albuterol use (1.1 vs 1.2 puffs per day, P = .03), and asthma-related quality of life (5.77 vs 5.59, P = .0004). Overweight/obese asthmatic subjects demonstrated a smaller improvement in exhaled nitric oxide levels with inhaled corticosteroid (ICS) treatment than did lean asthmatic subjects (3.6 vs 6.5 ppb, P = .04). With ICS/long-acting beta-agonist treatment, overweight/obese asthmatic subjects demonstrated smaller improvements in lung function than lean asthmatic subjects, with an 80 mL (P = .04) and 1.7% (P = .02) lesser improvement in FEV1 and FEV1/forced vital capacity ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed.ConclusionsIncreased BMI is not associated with clinically significant worsening of impairment in subjects with mild-to-moderate persistent asthma. There is a modest association between increased BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the effect of being overweight or obese on treatment response in asthma are warranted.
| S-EPMC2743451 | biostudies-literature
Project description: Not available
| S-EPMC11346270 | biostudies-literature