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The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

ABSTRACT: BACKGROUND:Acute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an increase in circulating Duffy-binding, proinflammatory chemokines like IL-8. We sought to determine the effect of the functional rs2814778 polymorphism, C/C genotype (Duffy null state), on clinical outcomes in African Americans with acute lung injury. METHODS:Clinical data and biologic specimens from African American patients with ALI who enrolled in three randomized controlled trials were analyzed. Multivariate analysis accounted for proportion of African ancestry, sex, cirrhosis, and severity of illness on presentation. RESULTS:Among 132 subjects, 88 (67%) were Duffy null (C/C genotype). The Duffy null state was associated with a 17% absolute risk increase (95% CI, 1.4%-33%) in mortality at 60 days, a median of 8 fewer ventilator-free days (95% CI, 1-18.5), and 4.5 fewer organ failure-free days (95% CI, 0-18) compared with individuals with the C/T or T/T genotypes (all P values < .05). Estimates were similar on multivariate analysis. In African Americans without the null variant, clinical outcomes were similar to those in patients of European descent. A subgroup analysis suggested that plasma IL-8 levels are increased in Duffy null individuals. CONCLUSIONS:Our results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8.

SUBMITTER: Kangelaris KN

PROVIDER: S-EPMC3342784 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

Kangelaris Kirsten Neudoerffer KN Sapru Anil A Calfee Carolyn S CS Liu Kathleen D KD Pawlikowska Ludmila L Witte John S JS Vittinghoff Eric E Zhuo Hanjing H Auerbach Andrew D AD Ziv Elad E Matthay Michael A MA

Chest 20111229 5

<h4>Background</h4>Acute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an i ...[more]

PMID: 22207676

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Project description:BACKGROUND:This retrospective study compared the change in serum creatinine between African American and Caucasian total knee arthroplasty (TKA) patients. The authors hypothesized that African Americans would demonstrate significantly greater change, and that a significantly greater proportion would demonstrate creatinine changes consistent with acute kidney injury (AKI). METHODS:Primary TKAs performed at a single institution between July 2011 and June 2016 were identified: 1035 primary TKAs met inclusion and exclusion criteria (110 African American, 925 Caucasian, excluding Hispanic and Asian patients). None were excluded based on gender, age, body mass index, preoperative diagnosis, or comorbidities. All patients had preoperative and postoperative creatinine levels available in the electronic medical records. Each patient received the same preop and postop protocol for nonsteroidal anti-inflammatory drug use along with other drugs administered including anesthesia. All patients received 1 g of intravenous vancomycin with some patients additionally receiving 1 g of vancomycin powder administered locally at the end of surgery. All patients were controlled for fluid intake and blood loss, along with no patient receiving a transfusion or intravenous contrast. Patient demographics and preoperative/postoperative serum creatinine were recorded and then analyzed for presence of AKI (?0.3 mg/dL). Preoperative/postoperative serum creatinine concentrations were compared between African American and Caucasian patients using 2 × 2 repeated measures analysis of variance. Prevalence of patients in each group demonstrating AKI was calculated using Fisher's exact test. RESULTS:African American patients had significantly greater serum creatinine preoperatively (1.00 ± 0.26 vs 0.90 ± 0.22, P < .001) and a significantly greater increase postoperatively (0.10 vs 0.03, P < .001). A significantly greater number of African American patients demonstrated AKI (10.9% vs 5.1%, P = .03). Furthermore, a significantly greater number of African American patients stayed in the hospital an additional 2 or more days for renal issues (2.7% vs 0.4%, P = .03). CONCLUSION:Altered renal function was significantly more common in African American TKA patients. Future studies are necessary to determine if tailoring anti-inflammatories, perioperative medications, and preoperative comorbidities reduce the risk of renal injury and/or a longer hospital stay for this subset of patients.

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Project description:BackgroundCyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer.MethodsThis study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations.ResultsThe lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism.ConclusionThis study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

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The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

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The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

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