Genetic variation influencing hemoglobin levels and risk for anemia across populations

Abstract

Hemoglobin (Hb) concentration is the outcome of the interaction between genetic variation and environmental factors, including nutritional status, sex, age, and altitude. Genetic diversity influencing this protein is complex and varies widely across populations. Variants related to abnormal Hb or altered characteristics of the erythrocytes increase the risk for anemia. The most prevalent are related to the inherited globin abnormalities affecting Hb production and structure. Malaria-endemic regions harbor the highest frequencies of variants associated with the most frequent monogenic diseases and the risk for nonnutritional anemia and are considered as public health problems. Variation in genes encoding for enzymes and membrane proteins in red blood cells also influence erythrocyte life span and risk for anemia. Most of these variants are rare. Interindividual variability of hematological parameters is also influenced by common genetic variation across the whole genome. Some of the identified variants are associated with Hb production, erythropoiesis, and iron metabolism. Specialized databases have been developed to organize and update the large body of available information on genetic variation related to Hb variation, their frequency, geographical distribution, and clinical significance. Our present review analyzed the underlying genetic factors that affect Hb concentrations, their clinical relevance, and geographical distribution across populations.

Diagnosing anemia: Challenges selecting methods, addressing underlying causes, and implementing actions at the public health level

“…A highly diverse genetic variation influences Hb concentrations and the risk for anemia. The variants with the largest effects and high frequency are within the HBA1 , HBA2 , and HBB genes and are major causes for anemia around the world 77 . Inherited genetic Hb disorders, particularly the thalassaemia trait and possibly the sickle cell trait, are one of the top three causes of anemia globally.…”

HbA1C as a marker of retrograde glycaemic control in diabetes patient with co‐existed beta‐thalassaemia: A case report and a literature review

“…It is composed of two α (141 amino acids) and two β (146 amino acids) chains. HbA2 is composed of two α and two δ chains and comprises 2.2%‐3.5% of an adult's haemoglobin . Inherited diseases that affect any part of haemoglobin components syntheses alter haemoglobin structure and biochemical properties with different physiological and clinical significance …”

“…3,4 Inherited diseases that affect any part of haemoglobin components syntheses alter haemoglobin structure and biochemical properties with different physiological and clinical significance. 1,3,4 Thalassaemia is a group of inherited diseases, characterized by abnormal production of one or more α or β globin chains with subsequent imbalance in haemoglobin (Hb) production. Red blood cells (RBC) in thalassaemia syndromes are prone to medullary or extramedullary haemolysis due to membrane damage induced by nonmatched globin chains.…”

Risk Association, Linkage Disequilibrium, and Haplotype Analyses of β-Like Globin Gene Polymorphisms with Malaria Risk in the Sabah Population of Malaysian Borneo

“…Interestingly, another SNP in the 5′ region of the β-globin gene, the C-551T (rs number is not available), is found as a silencer for the gene’s transcription and is associated with a thalassemic phenotype [ 9 ]. Furthermore, earlier research has linked the C16G (rs10768683) and G79A (rs33950507) SNPs in the globin gene to modifications in erythrocyte structure and thalassemia illness [ 10 , 11 , 12 ]. These SNPs are related to the function or structure of the red blood cells.…”