Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury

Hao, Jian Jun; He, Xiangjiu

doi:10.1186/1476-511x-13-79

Cited by 9 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accord with this, we found that the beneficial effect in septic shock of PCSK9 loss-of-function variants was abolished in patients with mutations of the LDLR gene near the site of usual PCSK9 binding to the LDLR (50). In addition, wild-type mice benefitted from (75) and genetic variants of ApoA1 are associated with sepsis-induced acute lung injury in one study (76).…”

Section: Central Role Of Pcsk9 In Pathogen Lipid Clearancementioning

confidence: 98%

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

Walley

Opal

Stein

et al. 2015

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Microbial cell walls contain pathogenic lipids, including LPS in gram-negative bacteria, lipoteichoic acid in gram-positive bacteria, and phospholipomannan in fungi. These pathogen lipids are major ligands for innate immune receptors and figure prominently in triggering the septic inflammatory response. Alternatively, pathogen lipids can be cleared and inactivated, thus limiting the inflammatory response. Accordingly, biological mechanisms for sequestering and clearing pathogen lipids from the circulation have evolved. Pathogen lipids released into the circulation are initially bound by transfer proteins, notably LPS binding protein and phospholipid transfer protein, and incorporated into high-density lipoprotein particles. Next, LPS binding protein, phospholipid transfer protein, and other transfer proteins transfer these lipids to ApoB-containing lipoproteins, including low-density (LDL) and very-low-density lipoproteins and chylomicrons. Pathogen lipids within these lipoproteins and their remnants are then cleared from the circulation by the liver. Hepatic clearance involves the LDL receptor (LDLR) and possibly other receptors. Once absorbed by the liver, these lipids are then excreted in the bile. Recent evidence suggests pathogen lipid clearance can be modulated. Importantly, reduced proprotein convertase subtilisin/kexin type 9 activity increases recycling of the LDLR and thereby increases LDLR on the surface of hepatocytes, which increases clearance by the liver of pathogen lipids transported in LDL. Increased pathogen lipid clearance, which can be achieved by inhibiting proprotein convertase subtilisin/kexin type 9, may decrease the systemic inflammatory response to sepsis and improve clinical outcomes.

show abstract

Section: Central Role Of Pcsk9 In Pathogen Lipid Clearancementioning

confidence: 98%

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

Walley

Opal

Stein

et al. 2015

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Carriage of the APOA1 -75 AA genotype in the APOA1 promoter, which has reduced promoter activity as compared to the major G allele, has been associated with a higher risk of ALI following cardiopulmonary bypass surgery ( Smith et al, 1992 ; Tu et al, 2013 ). The rs11216153 SNP in the APOA1 gene has also been associated with ALI risk in subjects with sepsis, with the GG genotype and G allele being more common among ALI patients than controls ( Hao and He, 2014 ). However, since this SNP is located in a non-coding region of the APOA1 gene, it is unclear if the association is with the APOA1 gene itself or variants from nearby genes.…”

Section: Acute Lung Injury (Ali) and Acute Respiratory Distress Syndrmentioning

confidence: 99%

High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

et al. 2016

View full text Add to dashboard Cite

Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol eﬄux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of ALI, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

show abstract

“…For rs2070665, the T allele frequency in the Kazakh control group was 32.5%. The allele mutation rate was higher than the foreign report (Henkhaus et al, 2011), but lower than the 42.0% of Chinese nationals reported by Hao and He (2014). The findings indicate that ethnic differences exist in the genotype and allele frequencies of this locus of the APOA1 gene.…”

Section: Discussionmentioning

confidence: 40%

Association of APOA1 gene polymorphisms (rs670, rs5069, and rs2070665) with dyslipidemia in the Kazakhs of Xinjiang

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of this study was to investigate the potential association between apolipoprotein A1 (APOA1) gene rs670, rs5069, and rs2070665 polymorphisms and dyslipidemia in the Kazakh population of Xinjiang, China. Matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify APOA1 (rs670, rs5069, and rs2070665) genotypes in 736 subjects (341 dyslipidemia patients and 395 control subjects). The frequencies of the CC genotype for rs1421085 were found to be 7.2% (obese group), 4.4% (overweight group), and 5.6% (control group). Polymorphisms of the three loci of the APOA1 gene in Kazakh subjects met Hardy-Weinberg equilibrium. The frequencies of the A allele for rs670 were found to be 14.3% (dyslipidemia group) and 12.7% (control group). The frequencies of the T allele for rs5069 and rs2070665 were: dyslipidemia group (7.2 and 30.1%, respectively) and control group (7.7 and 32.5%, respectively). Frequency distributions of the 3 types of genotypes and alleles of the three loci showed no statistically significant difference (P > 0.05). Significant differences were observed in lipoprotein (α) [Lp(α)] between patients with the rs2070665 CT + TT and CC genotypes (P < 0.05); however, none of the other relevant indicators differed significantly between the two genotypes. No significant association was identified between rs670 or rs5069 and the lipid-related metabolic indices assessed in the study. These findings indicate that the polymorphisms in the APOA1 gene (rs670, rs5069, and rs2070665) are not associated with dyslipidemia in the Kazakh population assessed in this study.

show abstract

Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury

Cited by 9 publications

References 30 publications

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

Association of APOA1 gene polymorphisms (rs670, rs5069, and rs2070665) with dyslipidemia in the Kazakhs of Xinjiang

Contact Info

Product

Resources

About