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TSLP and TSLP receptors variants are associated with smoking.

ABSTRACT: BACKGROUND:To search for new prevention markers for early detection of the diseases caused by tobacco, we aimed to investigate the polymorphisms in TSLP and TSLPRs associated with cigarette smoking in the Saudi population. MATERIALS AND METHODS:Samples were collected from 177 smokers and 126 healthy controls. Three TSLP SNPs [rs3806933, rs2289276, and rs10043985], three TSLPR SNPs [rs36133495, rs36177645, and rs36139698], and two IL7R SNPs rs1053496 and rs12516866 were analyzed by genotyping. RESULTS:Two TSLP SNPs (rs10043985 and rs3806933) and one TSLPR SNP (rs36139698) showed significant correlations with smoking behavior, but not IL7R rs12516866 and rs1053496. rs10043985 showed a clear association with long-term smoking regardless of daily cigarette consumption. rs2289276 was associated with short-term smoking but not with daily cigarette consumption. rs3806933 was highly associated with different smoker subgroups. Rs36139698 was highly associated with long-term smokers who consumed ?20 cigarettes/day, and the "T" allele was associated only with individuals who smoked ?20 cigarettes/day. Rs36139698 corresponds to a P195L substitution and produces a TSLPR mutant with a predicted ??G increase of 2.15 kcal/mol and has a more stable structure than the wild-type variant. CONCLUSIONS:Investigating TSLP and TSLPR polymorphisms is crucial for elucidating the mechanisms underlying tobacco-induced diseases.

SUBMITTER: Semlali A

PROVIDER: S-EPMC6687645 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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TSLP and TSLP receptors variants are associated with smoking.

Semlali Abdelhabib A Almutairi Mikhlid M Azzi Arezki A Reddy Parine Narasimha N AlAmri Abdullah A Alsulami Saleh S Meshal Alumri Talal T Saud Alanazi Mohammad M Rouabhia Mahmoud M

Molecular genetics & genomic medicine 20190709 8

<h4>Background</h4>To search for new prevention markers for early detection of the diseases caused by tobacco, we aimed to investigate the polymorphisms in TSLP and TSLPRs associated with cigarette smoking in the Saudi population.<h4>Materials and methods</h4>Samples were collected from 177 smokers and 126 healthy controls. Three TSLP SNPs [rs3806933, rs2289276, and rs10043985], three TSLPR SNPs [rs36133495, rs36177645, and rs36139698], and two IL7R SNPs rs1053496 and rs12516866 were analyzed by ...[more]

PMID: 31290290

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Project description:Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Project description: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.

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TSLP and TSLP receptors variants are associated with smoking.

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TSLP and TSLP receptors variants are associated with smoking.

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