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Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity

Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and... A previous expression profiling of VAT (visceral adipose tissue) revealed that the TSLP (thymic stromal lymphopoietin) gene was less expressed in severely obese men with ( n =7) compared with without ( n =7) the MetS (metabolic syndrome). We hypothesized that TSLP SNPs (single nucleotide polymorphisms) are associated with TSLP gene expression in VAT and with MetS phenotypes. Following validation of lower TSLP expression ( P =0.003) in VAT of severely obese men and women with ( n =70) compared with without ( n =60) the MetS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron–exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expression variability (ANOVAs) and then genotyped in two independent samples of severely obese men (total, n =389) and women (total, n =894). In a sex-stratified multistage experimental design, ANOVAs were performed to test whether tagging SNPs were associated with MetS components treated as continuous variables. We observed that the non-coding SNP rs2289277 was associated with TSLP mRNA abundance ( P =0.04), as well as with SBP (systolic BP (blood pressure)) ( P =0.004) and DBP (diastolic BP) ( P =0.0003) in men when adjusting for age, waist circumference, smoking and medication treating hypertension. These novel observations suggest that TSLP expression in VAT may partly explain the inter-individual variability for metabolic impairments in the presence of obesity and that specific SNPs (rs2289277 and/or correlating SNPs) may influence TSLP gene expression as well as BP in obese men. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Science Portland Press

Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity

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Publisher
Portland Press
Copyright
Copyright by Portland Press
ISSN
0143-5221
DOI
10.1042/CS20110584
pmid
22304237
Publisher site
See Article on Publisher Site

Abstract

A previous expression profiling of VAT (visceral adipose tissue) revealed that the TSLP (thymic stromal lymphopoietin) gene was less expressed in severely obese men with ( n =7) compared with without ( n =7) the MetS (metabolic syndrome). We hypothesized that TSLP SNPs (single nucleotide polymorphisms) are associated with TSLP gene expression in VAT and with MetS phenotypes. Following validation of lower TSLP expression ( P =0.003) in VAT of severely obese men and women with ( n =70) compared with without ( n =60) the MetS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron–exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expression variability (ANOVAs) and then genotyped in two independent samples of severely obese men (total, n =389) and women (total, n =894). In a sex-stratified multistage experimental design, ANOVAs were performed to test whether tagging SNPs were associated with MetS components treated as continuous variables. We observed that the non-coding SNP rs2289277 was associated with TSLP mRNA abundance ( P =0.04), as well as with SBP (systolic BP (blood pressure)) ( P =0.004) and DBP (diastolic BP) ( P =0.0003) in men when adjusting for age, waist circumference, smoking and medication treating hypertension. These novel observations suggest that TSLP expression in VAT may partly explain the inter-individual variability for metabolic impairments in the presence of obesity and that specific SNPs (rs2289277 and/or correlating SNPs) may influence TSLP gene expression as well as BP in obese men.

Journal

Clinical Science – Portland Press

Published: Jul 1, 2012

Keywords: blood pressure (BP), gene expression, genetic association study, metabolic syndrome, polymorphism, thymic stromal lymphopoietin (TSLP)

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