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This minor haemoglobin, which forms about 2\u20133% of the total, has no known physiological role, but has the interesting property of preventing polymerization of deoxy\u2010sickle haemoglobin. If it were possible to increase the level of HbA<jats:sub>2<\/jats:sub> sufficiently it could have a benefit in sickle cell disease similar to that of foetal haemoglobin. Moreover, HbA<jats:sub>2<\/jats:sub> is present in all erythrocytes, an advantage not found with foetal haemoglobin, which is heterocellularly expressed. The molecular basis of HbA<jats:sub>2<\/jats:sub> gene (<jats:italic><jats:styled-content style=\"fixed-case\">HBD<\/jats:styled-content><\/jats:italic>) expression is partially understood, and with new molecular tools, it might be possible to induce levels of HbA<jats:sub>2<\/jats:sub> that could be clinically important. However, high concentrations of this positively charged haemoglobin might damage the erythrocyte membrane; also, the reciprocal relationship of \u03b4\u2010 and \u03b3\u2010globin gene (<jats:italic><jats:styled-content style=\"fixed-case\">HBD<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HBG<\/jats:styled-content>1\/2<\/jats:italic>, respectively) expression might negate any benefit of increasing transcription of the former.<\/jats:p>","DOI":"10.1111\/bjh.13570","type":"journal-article","created":{"date-parts":[[2015,6,24]],"date-time":"2015-06-24T06:54:40Z","timestamp":1435128880000},"page":"781-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["HbA<sub>2<\/sub>: biology, clinical relevance and a possible target for ameliorating sickle cell disease"],"prefix":"10.1111","volume":"170","author":[{"given":"Martin 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