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The mysterious power of blood: How do hemoglobin variations affect your health?
Hemoglobinopathies refer to a group of inherited blood disorders involving hemoglobin, a key protein in red blood cells that is responsible for oxygen transport. These disorders are usually inherited in a monogenic manner and most often follow an autosomal recessive inheritance pattern. Hemoglobinopathies can be divided into two main categories: structural abnormalities caused by mutations in the hemoglobin gene and thalassemias caused by insufficient production of normal hemoglobin molecules. The major hemoglobin structural variations include HbS, HbE, and HbC, while the major thalassemia types are divided into α-thalassemia and β-thalassemia.
Function of hemoglobin
Hemoglobin is an iron-containing protein that facilitates oxygen transport in red blood cells. It carries oxygen from the lungs to other tissues in the body that need it for aerobic respiration, which drives metabolism. Normal hemoglobin levels vary by sex and age, ranging between 9.5 and 17.2 grams per deciliter of blood. Hemoglobin can also transport other gases. About 20-25% of carbon dioxide is transported to the lungs in the form of carboxyhemoglobin.
Structural Biology of Hemoglobin
Normal human hemoglobin is a tetrameric protein composed of two pairs of globin chains, each of which contains an iron-containing heme group. Throughout life, the synthesis of α and β chains is relatively balanced, maintaining this ratio and preventing an excess of either type of chain. The specific α and β chains are tightly regulated during development:
Classification of HemoglobinopathiesEmbryonic hemoglobin begins to be expressed between four and six weeks of embryonic development and disappears around the eighth week of pregnancy, replaced by fetal hemoglobin.
A) Abnormal quality
Structural Abnormality
Hemoglobin structural variation can lead to changes in the structure of hemoglobin molecules. Most hemoglobin variants do not cause disease and are usually discovered incidentally during newborn screening. Hemoglobin variants can usually be detected by protein detection methods such as electrophoresis, isoelectric focusing, or high-performance liquid chromatography. The diagnosis is usually confirmed by DNA sequencing.
Sickle cell disease is the most common hemoglobinopathy. Sickle hemoglobin (HbS) tends to polymerize when deoxygenated, leading to damage and premature destruction of red blood cell membranes.
Chemical anomalies
Methemoglobinemia is a condition caused by high levels of the protein methemoglobin in the blood. Methemoglobin cannot bind oxygen and therefore cannot transport oxygen to tissues. Methemoglobin is produced spontaneously in human blood in trace amounts, and methemoglobin reductase is responsible for converting it into normal hemoglobin.
B) Abnormal production
Thalassemia
Thalassemia is a production defect that results in a reduction in the amount of a certain type of globulin chain, thereby disrupting the balance between the alpha and beta chains. This ratio is normally tightly regulated to prevent the accumulation of excess amounts of one class of globin chains. The clinically important subtypes of thalassemia are α-thalassemia and β-thalassemia.
Hemoglobin variationHemoglobin variations are not necessarily pathological. For example, Hb Lepore-Boston and G-Waimanalo are two cases without pathological variants.
There are more than 1,000 known hemoglobin variants, and Pennsylvania State University maintains a research database on hemoglobin variants.
Evolutionary Advantages
Certain hemoglobinopathies appear to provide an evolutionary advantage to people carrying the abnormal hemoglobin trait in areas where malaria is endemic. Malaria parasites infect red blood cells but subtly disrupt normal cell function and alter immune responses. Many mechanisms have been proposed to explain the increased chance of survival in individuals carrying the abnormal hemoglobin trait.
Do you know enough about hemoglobin variation and how it will affect your health?
