{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:30:12Z","timestamp":1789029012925,"version":"build-2803163510"},"reference-count":31,"publisher":"BMJ","issue":"11","funder":[{"name":"Shanghai Municipal Science and Technology Major Project","award":["2017SHZDZX01"],"award-info":[{"award-number":["2017SHZDZX01"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871265"],"award-info":[{"award-number":["31871265"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2022,7,12]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Reactivation of embryonic \u03b6-globin is a promising strategy for genetic treatment of \u03b1-thalassaemia. However, quantification of \u03b6-globin as a quantitative trait in \u03b1-thalassaemia carriers and patients remains incompletely understood. In this study, we aimed to set up a reliable approach for the quantification of \u03b6-globin in \u03b1-thalassaemia carriers, followed by a population study to investigate its expression patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      \u03b6-globin was purified as monomers from cord blood haemolysate of a Hb Bart\u2019s fetus, followed by absolute protein quantification, which was then tested by in-house ELISA system and introduced as protein standard. It was then used for large-scale quantification in peripheral blood samples from 6179 individuals. Finally, liquid chromatography-tandem mass spectrometry (LC-MS\/MS) introduced as an independent validating approach by measuring \u03b6-globin expression in a second cohort of 141\n                      <jats:sup>-SEA<\/jats:sup>\n                      \/\u03b1\u03b1 carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ELISA system was proved sensitive in distinguishing individuals with varied extent of \u03b6-globin. Large scale quantitative study of this --\n                      <jats:sup>SEA<\/jats:sup>\n                      \/\u03b1\u03b1 carrier cohort indicated the high diversity of \u03b6-globin expression ranging from 0.00155 g\/L to 1.48778 g\/L. Significant positive correlation between ELISA and LC-MS\/MS (R=0.400, p&lt;0.001) was observed and it is more sensitive in distinguishing the samples with extreme expression of \u03b6-globin (R=0.650, p&lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study has reported reliable approaches for the quantification of \u03b6-globin and presented the expression patterns of \u03b6-globin among the --\n                      <jats:sup>SEA<\/jats:sup>\n                      \/\u03b1\u03b1 carrier population, which might lay a foundation on subsequent genotype\u2013phenotype studies on mechanisms of delayed haemoglobin switch in \u03b1-thalassaemia.\n                    <\/jats:p>\n                  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