Dataset Information

Genetic variants of TSLP and asthma in an admixed urban population.

ABSTRACT: Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. METHODOLOGY AND MAIN RESULTS: Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR)?=?1.50; 95% confidence interval (95% CI): 1.09-2.05, p?=?0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR?=?2.00, 95% CI: 1.04-3.83, p?=?0.04) but not significant in never-smokers (OR?=?1.34; 95% CI: 0.93-1.94, p?=?0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR?=?1.58, 95% CI: 1.10-2.27, p?=?0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR?=?1.15, 95% CI: 1.07-1.23, p?=?0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR?=?1.21, 95% CI: 1.08-1.34, p?=?0.003; never-smokers: OR?=?1.06, 95% CI: 0.94-1.17, p?=?0.33).Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.

SUBMITTER: Liu M

PROVIDER: S-EPMC3178593 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Genetic variants of TSLP and asthma in an admixed urban population.

Liu Mengling M Rogers Linda L Cheng Qinyi Q Shao Yongzhao Y Fernandez-Beros Maria Elena ME Hirschhorn Joel N JN Lyon Helen N HN Gajdos Zofia K Z ZK Vedantam Sailaja S Gregersen Peter P Seldin Michael F MF Bleck Bertram B Ramasamy Adaikalavan A Hartikainen Anna-Liisa AL Jarvelin Marjo-Riitta MR Kuokkanen Mikko M Laitinen Tarja T Eriksson Johan J Lehtimäki Terho T Raitakari Olli T OT Reibman Joan J

PloS one 20110922 9

<h4>Background</h4>Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in ...[more]

PMID: 21966427

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Project description:Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease-associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges for further efforts to map disease-causing genes. This review, summarizes the historical context of admixed populations and AM, and considers current opportunities to use AM to map asthma genes. In addition, we provide an overview of the potential limitations and future directions of AM in biomedical research, including joint admixture and association mapping for asthma and asthma-related disorders.

Project description:BackgroundRates of asthma in Jordan have been doubled in the past decade, but this increased prevalence was not met with improved asthma control protocols. The aim of the present study was to assess whether there was any significant association between the level of asthma control and certain single-nucleotide polymorphisms (SNPs) in five genes: (ADRB2; rs1042713 and rs1042714), (CRHR1; rs1876828, rs242939, and rs242941), (STIP1; rs2236647), (ADH5, rs1154400), and (ARG1; rs2781659). These SNPs were selected based on their involvement in enzymes and receptors that are related to asthma pathways and subsequent response to medication and based on a high degree of linkage disequilibrium.Patients and methodsA cross-sectional genetic association study was conducted from June 2016 to June 2017 in the two major hospitals in Jordan. The present study involved sampling from adult asthmatic patients of Arab descent who were selected from two phenotypic groups, ie, controlled and uncontrolled asthma. The blood samples and medical data were collected from the participants. DNA samples were extracted, quantified, and genotyped according to standard operating procedure. Allelic and haplotypic analyses were performed using the Haploview®.ResultsA total of 245 Arab asthmatic patients were enrolled in this study. Genotyping analysis revealed that the two SNPs (rs1042713 and rs1042714) in ADRB2 gene, along with their related haplotypes, were nominally significantly associated with asthma control in the Jordanian population. The A-allele of rs1042713 and the C-allele of rs1042714 were more common in the uncontrolled asthma group than in the controlled asthma group (P=0.048 and P=0.017, respectively).ConclusionThis was the first study that identified the nominal significant association between the level of asthma control and genetic variants in ADRB2 gene in Arab population. Further studies in other Arab region with larger sample size are recommended to confirm the relationship.

Dataset Information

Genetic variants of TSLP and asthma in an admixed urban population.

Publications

Genetic variants of TSLP and asthma in an admixed urban population.

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