Genetic interaction of Hsp70 family genes polymorphisms with high-altitude pulmonary edema among Chinese railway constructors at altitudes exceeding 4000 meters

Qi, Yue; Niu, Wenquan; Zhu, Tongchun; Liu, Jingliang; Dong, Wei-Ya; Xu, Ying; Ding, Shou-quan; Cui, Cheng-Bing; Pan, Yunjun; Yu, Guo-shu; Zhou, Wu-qing; Qiu, Changchun

doi:10.1016/j.cca.2009.03.056

Cited by 35 publications

(29 citation statements)

References 26 publications

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“…Based on our results, homozygosity for −110A/C and +190 G/C SNPs entails a risk of presenting moderate vascular risk or declared atherosclerosis-probably as a result of diminished intracellular HSPA1A synthesis and a consequent partial loss of its antiinflammatory and antithrombotic properties. Previous studies evaluating the activity of the promoter of HSPA1A gene through luciferase reporter assays have demonstrated that polymorphism rs1008438 modifies the activity of the promoter, the −110A allele showing significantly higher promoter activity than the −110 C allele (Qi et al 2009). He et al (2009) demonstrated that the +190 C allele is also associated to a reduction in relative luciferase activity (RLA), from which it can be concluded that the +190 C allele in the 5′UTR region of the HSPA1A gene reduces the activity of the promoter and probably diminishes HSPA1A protein synthesis through translation efficiency or post-transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis

Dulín

García‐Barreno

Guisasola

2012

Cell Stress and Chaperones

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HSPA1A is a serum and intracellular heat shock protein with antiapoptotic and antithrombotic properties. The present study examines the hypothesis that a decrease in the synthesis of this protein in relation to certain polymorphisms of the regulatory region of the HSPA1A gene can define a vascular disease risk phenotype. A randomly selected population was studied and stratified into groups according to the degree of vascular risk. After applying the Task Force Chart to 452 people, the subjects were divided into three groups: group 0 (no vascular risk factor or risk<5%), n0239; group 1 (moderate (10-20%) risk, with no clinical cardiovascular disease), n0161; and group 2 (overt atherosclerosis), n052. Serum and intragranulocytic HSPA1A was quantified, and direct Sanger sequencing was performed in all subjects. An analysis was made of the association of two single nucleotide polymorphisms (db rs1008438 −110A/C and db rs1043618 +190 G/C) with circulating and intragranulocytic HSPA1A and the risk of atherosclerosis. The atherosclerotic subjects showed significantly lower circulating HSPA1A levels than the other groups, regardless of the genotype. The patients with CC genotype for both polymorphisms showed significantly lower intragranulocytic HSPA1A levels than the other genotypes. Serum HSPA1A concentrations could be proposed as a biomarker of cardiovascular disease. CC homozygosis for polymorphisms db rs1008438 and db rs1043618 is associated with a decrease in the intragranulocytic production of HSPA1A. Given the antiatherogenic functions of intracellular HSPA1A, the −110A and +190 G alleles could constitute potential genetic biomarkers of a less severe clinical phenotype for the risk of developing atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis

Dulín

García‐Barreno

Guisasola

2012

Cell Stress and Chaperones

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“…Genetic variations in additional genes implicated in hypoxia-induced responses (Mortimer et al, 2004), including those of pulmonary surfactant proteins A1 and A2 (Saxena et al, 2005) and the Hsp70 family (Qi et al, 2009), have also been proposed to be associated with HAPE susceptibility. However, SNPs of tyrosine hydroxylase (Hanaoka et al, 2003) and vascular endothelial growth factor (Hanaoka et al, 2009) were not associated with HAPE susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese

Luo¹,

Gao²,

Li³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. High-altitude pulmonary edema (HAPE) is a lifethreatening condition caused by acute exposure to high altitude. Accumulating evidence suggests that genetic factors play an important role in the etiology of HAPE. However, conclusions from association studies have been hindered by limited sample size due to the rareness of this disease. It is known that mitochondria are critical for hypoxic adaptation, and mitochondrial malfunction can be an important factor in HAPE development. Therefore, we tested the hypothesis that ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 3658-3667 (2012) Mitochondrial haplogroup and HAPE susceptibility 3659 mitochondrial DNA haplotypes and polymorphisms affect HAPE susceptibility. We recruited 204 HAPE patients and 174 healthy controls in Tibet (3658 m above sea level), all Han Chinese, constituting the largest sample size of all HAPE vulnerability studies. Among mtDNA haplogroups, we found that haplogroup D4 is associated with resistance to HAPE, while haplogroup B is a genetic risk factor for this condition. Haplogroup D4 (tagged by 3010A) may enhance the stability of 16S rRNA, resulting in reduced oxidative stress and protection against HAPE. Within haplogroup B, subhaplogroup B4c (tagged by 15436A and 1119C) was associated with increased risk for HAPE, while subhaplogroup B4b may protect against HAPE. We indicate that there are differences in HAPE susceptibility among mtDNA haplogroups. We conclude that mitochondria are involved in adverse reactions to acute hypoxic exposure; our finding of differences in susceptibility as a function of mitochondrial DNA haplotype may shed light on the pathogenesis of other disorders associated with hypoxia, such as chronic obstructive pulmonary disease.

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“…The diplotype, Dip 5 (Hap1-Hap7) was also reported to have an increased susceptibility to HAPE [15]. Also, rs1061581, rs1043618 and rs1008438 polymorphisms within Hsp70 family caused HAPE-susceptibility in Chinese with polymorphism rs1008438 causing a change in HSPA1A promoter activity and potentially leading to HAPE development [15]. HSP1A and HSP1B genes have also been found to be associated with HAPEsusceptibility [14].…”

Section: A) Polymorphism In Genes Involved In Hypoxia Signalingmentioning

confidence: 99%

“…Another study on Chinese railway construction workers found that haplotype Hap 4 (G-C-A, in order of rs1061581, rs1043618 and rs1008438) and Hap 5 (G-G-A) had an 86% reduced risk, whereas Hap 7 (A-C-C) had a 2.43-fold increased risk for HAPE. The diplotype, Dip 5 (Hap1-Hap7) was also reported to have an increased susceptibility to HAPE [15]. Also, rs1061581, rs1043618 and rs1008438 polymorphisms within Hsp70 family caused HAPE-susceptibility in Chinese with polymorphism rs1008438 causing a change in HSPA1A promoter activity and potentially leading to HAPE development [15].…”

Section: A) Polymorphism In Genes Involved In Hypoxia Signalingmentioning

confidence: 99%

“…The risk factors associated with development of HAPE are the rate of ascent ( >350 m per day above 2000 m), the genetic and physiological constitution of the individual, race and family of the individual, the altitude traversed (especially sleeping altitude), any previous history of HAPE, exertion/exercise (particularly high-intensity exercise), cold, administration/intake of any sedatives, any recent infections or disease affecting the lower airways and an idiopathic tendency of pulmonary hypertension [9,[13][14][15][16][17][18][19].…”

Section: Symptoms and Risk Factorsmentioning

confidence: 99%

See 1 more Smart Citation

High Altitude Pulmonary Edema: An Update on Omics Data and Redefining Susceptibility

Gangwar¹

2015

J Proteomics Bioinform

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Genetic interaction of Hsp70 family genes polymorphisms with high-altitude pulmonary edema among Chinese railway constructors at altitudes exceeding 4000 meters

Cited by 35 publications

References 26 publications

Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis

Genetic variations of HSPA1A, the heat shock protein levels, and risk of atherosclerosis

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese

High Altitude Pulmonary Edema: An Update on Omics Data and Redefining Susceptibility

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