Dataset Information

Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome.

ABSTRACT: Epidermal growth factor (EGF) is involved in alveolar epithelial repair, lung fluid clearance and inflammation, and is regulated by sex hormones. An unmatched, nested case-control study was conducted to evaluate the associations of EGF variants with acute respiratory distress syndrome (ARDS) and the role of sex on the associations between EGF variants and ARDS. Patients with ARDS risk factors upon intensive care unit admission were enrolled. Cases were 416 Caucasians who developed ARDS and controls were 1,052 Caucasians who did not develop ARDS. Cases were followed for clinical outcomes and 60-day mortality. One functional single nucleotide polymorphism (SNP), rs4444903, and six haplotype-tagging SNPs spanning the entire EGF gene were genotyped. No individual SNP or haplotype was associated with ARDS risk or outcomes in all subjects. Sex-stratified analyses showed opposite effects of EGF variants on ARDS in males versus in females. SNPs rs4444903, rs2298991, rs7692976 and rs4698803, and haplotypes GGCGTC and ATCAAG were associated with ARDS risk in males. No associations were observed in females. Interaction analysis showed that rs4444903, rs2298991, rs7692976 and rs6533485 significantly interacted with sex for ARDS risk. The present study suggests that associations of epidermal growth factor gene variants with acute respiratory distress syndrome risk are modified by sex. The current findings should be replicated in other populations.

SUBMITTER: Sheu CC

PROVIDER: S-EPMC2747588 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome.

Sheu C C CC Zhai R R Su L L Tejera P P Gong M N MN Thompson B T BT Chen F F Christiani D C DC

The European respiratory journal 20081114 3

Epidermal growth factor (EGF) is involved in alveolar epithelial repair, lung fluid clearance and inflammation, and is regulated by sex hormones. An unmatched, nested case-control study was conducted to evaluate the associations of EGF variants with acute respiratory distress syndrome (ARDS) and the role of sex on the associations between EGF variants and ARDS. Patients with ARDS risk factors upon intensive care unit admission were enrolled. Cases were 416 Caucasians who developed ARDS and contr ...[more]

PMID: 19010984

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Project description:RationaleAdiponectin is an anti-inflammatory adipokine that is the most abundant gene product of adipose tissue. Lower levels have been observed in obesity, insulin resistance, and in critical illness. However, elevated levels early in acute respiratory failure have been associated with mortality. Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined for relationships with obesity, insulin resistance and diabetes, cardiovascular disease, and to circulating adipokine levels, but many gaps in knowledge remain. The current study aims to assess the association between potentially functional polymorphisms in adiponectin-related genes with acute respiratory distress syndrome (ARDS) risk and mortality.MethodsConsecutive patients with risk factors for ARDS admitted to the ICU were enrolled and followed prospectively for development of ARDS. ARDS cases were followed through day 60 for all-cause mortality. 2067 patients were successfully genotyped using the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed ARDS. Forty-four single nucleotide polymorphisms (SNPs) on ADIPOQ, ADIPOR1 and ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be functional based on their location (promoter, exon, or 3' untranslated region). These 9 SNPs were analyzed for association with ARDS case status and mortality among ARDS cases.ResultsAfter multivariable analysis and adjustment for multiple comparisons, no SNPs were significantly associated with ARDS case status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ) had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36-5.00, p = 0.0039) after adjustment for significant covariates. The significance of this association persisted after adjustment for multiple comparisons (FDR_q = 0.029).ConclusionsA common and potentially functional polymorphism in ADIPOQ may impact survival in ARDS. Further studies are required to replicate these results and to correlate genotype with circulating adiponectin levels.

Dataset Information

Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome.

Publications

Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome.

Similar Datasets

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