Background: Recent studies have suggested that thymic stromal lymphopoietin (TSLP), a key cytokine involved in the dendritic cell-mediated activation of Th2-mediated inflammatory responses, is significantly increased in nasal polyps from atopic individuals. Our objective was therefore to explore firstly any associations between single nucleotide polymorphisms (SNPs) in and around the TSLP gene and development of chronic rhinosinusitis (CRS; with (CRSwNP) or without (CRSsNP) nasal polyps and, and secondly the influence of nasal polyposis and gender. Methods: A population-based case-control association analysis was performed in a Han Chinese cohort. DNA extracted from peripheral blood leukocytes from 638 subjects with CRS (306 CRSwNP and 332 CRSsNP) and 325 healthy controls was assessed for 11 SNPs in and around TSLP gene, selected from the Chinese HapMap genotyping dataset. Genetic association tests were performed using the Haploview and STATA software package. Results: Single-locus analysis of CRS risk, showed no significant differences in allele or genotype frequencies between CRS subjects and controls. Stratified analyses of association between the selected SNPs and CRS adjusted for gender demonstrated that rs13156068 (CC genotype: P = 0.010, OR = 0.289) and rs764917 (CC genotype: P = 0.040, OR=0.509) were significantly protective against CRS, whereas rs6886755 (GT genotype: P = 0.040, OR = 0.509) presented a risk among females. In contrast, rs764917 (CA genotype: P = 0.033, OR=1.553) presented risk for CRS in males. Furthermore, SNPs rs252706 (AA genotype: P = 0.012, OR = 0.552) and rs764917 (CA genotype: P = 0.001, OR = 0.182) displayed protective roles among CRSwNP, but not CRSsNP, subjects. Conclusions: This study suggests that SNPs in TSLP gene may exert a gender and/or nasal polyposis-dependent risk for development of CRS in Chinese subjects. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.