Hb Grove City [β38(C4)Thr→Ser, ACC&gt;AGC;HBB: c.116C&gt;G]: A New Low Oxygen Affinity β Chain Variant

Taliercio, Rachel M.; Ashton, Rendell W.; Horwitz, Leonard; Swanson, Kenneth C.; Wendt, Patricia; Hoyer, James D.; Oliveira, Jennifer L.

doi:10.3109/03630269.2013.789794

Cited by 7 publications

(5 citation statements)

References 8 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparison of HBB expression between Tibetan pigs and Landrace pigs showed that among the beta globin amino acid substitutions at positions 58, 75, 119 and 137, the replacement of alanine at position 137 with valine and the locus mutation improved the affinity of HGB and O 2 (Zhang B. et al, 2016). The expression of the HBB gene in Tibetan pigs (TH and TL) was significantly higher than that in Landrace pigs (LH and LL), agreeing with a similar trend previously reported by other authors, and there was similar variation in the HGB concentration in Tibetan pigs (Taliercio et al, 2013;Zhang B. et al, 2016;Yang et al, 2021), indicating that hypoxia transcriptionally upregulates HBB to increase HGB in the blood to ensure the transport of blood and nutrients. These findings may (Jang et al, 2014;Cai et al, 2018) explain why Tibetan pigs have better adaption than Landrace pigs in hypoxic environments regardless of altitude.…”

Section: Discussionsupporting

confidence: 88%

The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

et al. 2021

View full text Add to dashboard Cite

To adapt to a low-oxygen environment, Tibetan pigs have developed a series of unique characteristics and can transport oxygen more effectively; however, the regulation of the associated processes in high-altitude animals remains elusive. We performed mRNA-seq and miRNA-seq, and we constructed coexpression regulatory networks of the lung tissues of Tibetan and Landrace pigs. HBB, AGT, COL1A2, and EPHX1 were identified as major regulators of hypoxia-induced genes that regulate blood pressure and circulation, and they were enriched in pathways related to signal transduction and angiogenesis, such as HIF-1, PI3K-Akt, mTOR, and AMPK. HBB may promote the combination of hemoglobin and oxygen as well as angiogenesis for high-altitude adaptation in Tibetan pigs. The expression of MMP2 showed a similar tendency of alveolar septum thickness among the four groups. These results indicated that MMP2 activity may lead to widening of the alveolar wall and septum, alveolar structure damage, and collapse of alveolar space with remarkable fibrosis. These findings provide a perspective on hypoxia-adaptive genes in the lungs in addition to insights into potential candidate genes in Tibetan pigs for further research in the field of high-altitude adaptation.

show abstract

Section: Discussionsupporting

confidence: 88%

The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…There was no evidence of hemolytic anemia in the individuals we described in this case. However, Hb Grove City (a beta chain Hb variant) was described in a woman and her daughter who both presented with hypoxemia and mild anemia, somewhat similar to our case [ 18 ].…”

Section: Discussionsupporting

confidence: 78%

Hemoglobin Alpha Chain Variant Zara Associated With Familial Asymptomatic Hypoxemia

Pasquarella¹,

Miller²,

Wong³

et al. 2022

J Hematol

View full text Add to dashboard Cite

Numerous hemoglobin (Hb) gene mutations have been identified, leading to a spectrum of phenotypes ranging from asymptomatic carrier states to complicated hemolytic anemias. We report a rare case of asymptomatic hypoxemia in a father and his teenage daughter both of whom were found to be carriers of Hb gene variant Zara. Workup for alternative cardiovascular causes of hypoxemia was unremarkable. Further sequencing of the alpha globin locus showed both individuals to be heterozygous for the Hb Zara c.274C>A (p.Leu92Ile) variant of unknown significance in the alpha2-globin gene. This is the first documented association of this Hb variant with familial asymptomatic hypoxemia, highlighting the importance of evaluating for hemoglobinopathies in patients with reduced oxygen saturation.

show abstract

“…Interestingly, there are numerous reported cases worldwide of rare human Hb variants with permanently altered Hb binding affinity (Fairbanks et al 1971;Jones & Shih, 1980;Hoyer et al 1998;Oliveira et al 2010;Hoyer et al 2011;Inoue et al 2012;Szuberski et al 2012;Taliercio et al 2013;Collier et al 2016;Oliveira et al 2018). Specifically, genetic mutations in the variants' amino acid sequence of the alpha or beta Hb chains can phenotypically manifest as Hb with altered ODCs (P 50 ranging from Hb-Syracuse at 11 mmHg to Hb-Kansas at 48 mmHg).…”

Section: Introductionmentioning

confidence: 99%

Modelling the relationships between haemoglobin oxygen affinity and the oxygen cascade in humans

Shepherd

Dominelli

Roy

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Haemoglobin affinity is an integral concept in exercise physiology that impacts oxygen uptake, delivery and consumption. How chronic alterations in haemoglobin affinity impact physiology is unknown. Using human haemoglobin variants, we demonstrate that the affinity of haemoglobin for oxygen is highly correlated with haemoglobin concentration. Using the Fick equation, we model how altered haemoglobin affinity and the associated haemoglobin concentration influences oxygen consumption at rest and during exercise via alterations in cardiac output and mixed‐venous PnormalO2. The combination of low oxygen affinity haemoglobin and reduced haemoglobin concentration seen in vivo may be unable to support oxygen uptake during moderate or heavy exercise. Abstract The physiological implications, with regard to exercise, of altered haemoglobin affinity for oxygen are not fully understood. Data from the Mayo Clinic Laboratories database of rare human haemoglobin variants reveal a strong inverse correlation (r = −0.82) between blood haemoglobin concentration and P50, an index of oxygen affinity [Hb = −0.3135(P50) + 23.636]. In the present study, observed P50 values for high, normal and low oxygen‐affinity haemoglobin variants (13, 26 and 39 mmHg) and corresponding haemoglobin concentrations (19.5, 15.5 and 11.4 g dL−1 respectively) are used to model oxygen consumption as a fraction of delivery at rest (V̇O2 = 0.25 L min−1, cardiac output = 5.70 L min−1) and during exercise (V̇O2 = 2.75 L min−1, cardiac output = 18.9 l min−1). With high‐affinity haemoglobin, the model shows that normal levels of oxygen consumption can be achieved at rest and during exercise at the assumed cardiac output levels, with reduced oxygen extraction both at rest (16.8% high affinity vs. 21.7% normal) and during exercise (55.8% high affinity vs. 72.2% normal). With low‐affinity haemoglobin, which predicts low haemoglobin concentration, oxygen consumption at rest can be sustained with the assumed cardiac output, with increased oxygen extraction (31.1% low affinity vs. 21.7% normal). However, exercise at 2.75 l min−1 cannot be achieved with the assumed cardiac output, even with 100% oxygen extraction. In conclusion, the model indicates chronic alterations in P50 associate directly with Hb concentration, highlighting that human Hb variants can serve as ‘experiments of nature’ to address fundamental hypotheses on oxygen transport and exercise.

show abstract

Hb Grove City [β38(C4)Thr→Ser, ACC>AGC;HBB: c.116C>G]: A New Low Oxygen Affinity β Chain Variant

Cited by 7 publications

References 8 publications

The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

Hemoglobin Alpha Chain Variant Zara Associated With Familial Asymptomatic Hypoxemia

Modelling the relationships between haemoglobin oxygen affinity and the oxygen cascade in humans

Contact Info

Product

Resources

About