Dataset Information

Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

ABSTRACT: BACKGROUND:Convincing evidences have demonstrated the associations between HHIP and FAM13a polymorphisms and COPD in non-Asian populations. Here genetic variants in HHIP and FAM13a were investigated in Southern Han Chinese COPD. METHODS:A case-control study was conducted, including 989 cases and 999 controls. The associations between SNPs genotypes and COPD were performed by a logistic regression model; for SNPs and COPD-related phenotypes such as lung function, COPD severity, pack-year of smoking, and smoking status, a linear regression model was employed. Effects of risk alleles, genotypes, and haplotypes of the 3 significant SNPs in the HHIP gene on FEV1/FVC were also assessed in a linear regression model in COPD. RESULTS:The mean FEV1/FVC% value was 46.8 in combined COPD population. None of the 8 selected SNPs apparently related to COPD susceptibility. However, three SNPs (rs12509311, rs13118928, and rs182859) in HHIP were associated significantly with the FEV1/FVC% (Pmax = 4.1 × 10-4) in COPD adjusting for gender, age, and smoking pack-years. Moreover, statistical significance between risk alleles and the FEV1/FVC% (P = 2.3 × 10-4), risk genotypes, and the FEV1/FVC% (P = 3.5 × 10-4) was also observed in COPD. CONCLUSIONS:Genetic variants in HHIP were related with FEV1/FVC in COPD. Significant relationships between risk alleles and risk genotypes and FEV1/FVC in COPD were also identified.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5591965 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

Zhang Zili Z Wang Jian J Zheng Zeguang Z Chen Xindong X Zeng Xiansheng X Zhang Yi Y Li Defu D Shu Jiaze J Yang Kai K Lai Ning N Dong Lian L Lu Wenju W

BioMed research international 20170827

<h4>Background</h4>Convincing evidences have demonstrated the associations between <i>HHIP</i> and <i>FAM13a</i> polymorphisms and COPD in non-Asian populations. Here genetic variants in <i>HHIP</i> and <i>FAM13a</i> were investigated in Southern Han Chinese COPD.<h4>Methods</h4>A case-control study was conducted, including 989 cases and 999 controls. The associations between SNPs genotypes and COPD were performed by a logistic regression model; for SNPs and COPD-related phenotypes such as lung ...[more]

PMID: 28929109

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Project description:BACKGROUND:Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness. OBJECTIVE:To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort. DESIGN:Cross-sectional study. SETTING:Veterans Affairs Medical Center. PARTICIPANTS:A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health. METHODS:Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered. MAIN OUTCOME MEASUREMENTS:forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS:There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV1/FVC or between plasma adiponectin with FEV1, FVC, or FEV1/FVC. CONCLUSION:Plasma leptin in individuals with chronic SCI is inversely associated with FEV1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI. LEVEL OF EVIDENCE:II.

Project description:ImportanceAccording to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial.ObjectiveTo determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality.Design, setting, and participantsThe National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016.ExposuresPresence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN).Main outcomes and measuresThe primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach.ResultsAmong 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models.Conclusions and relevanceDefining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Dataset Information

Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

Publications

Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

Similar Datasets

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