{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:44:57Z","timestamp":1770705897127,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T00:00:00Z","timestamp":1385596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic haemolysis stands out as one of the hallmarks of sickle cell anaemia, a clinically heterogeneous autosomal recessive monogenic anaemia. However, the genetic architecture of this sub\u2010phenotype is still poorly understood. Here, we report the results of an association study between haemolysis biomarkers (serum <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content>, total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants of ten candidate genes in a series of 99 paediatric <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> patients (median current age of 9.9\u00a0yr) followed up in two general hospitals in <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>reater <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>isboa area (median follow\u2010up per patient of 5.0\u00a0yr). Although in a large number of tests a seemingly significant (i.e. <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) association was observed, the following ones were confirmed upon correction for multiple comparisons: (i) an increased serum <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> level was associated with haplotype 7 within <jats:italic><jats:styled-content style=\"fixed-case\">VCAM<\/jats:styled-content>1<\/jats:italic> gene; (ii) a lower total bilirubin was associated with the 3.7\u2010kb deletion at <jats:italic><jats:styled-content style=\"fixed-case\">HBA<\/jats:styled-content><\/jats:italic> gene, rs2070744_T allele at <jats:italic><jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>3<\/jats:italic> gene, and haplotype 9 within <jats:italic><jats:styled-content style=\"fixed-case\">VCAM<\/jats:styled-content>1<\/jats:italic> promoter; and (iii) a diminished reticulocyte count was associated with the 3.7\u2010kb deletion at <jats:italic><jats:styled-content style=\"fixed-case\">HBA<\/jats:styled-content><\/jats:italic>, whereas an increased count was associated with rs1984112_G allele at <jats:italic><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>36<\/jats:italic> gene. On the whole, our findings suggest a complex genetic architecture for the sickle cell anaemia haemolysis process involving multiple pathways, namely control of vascular cell adhesion, <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> synthesis and erythrocyte volume and haemoglobinisation.<\/jats:p>","DOI":"10.1111\/ejh.12226","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T08:58:22Z","timestamp":1383037102000},"page":"237-243","source":"Crossref","is-referenced-by-count":14,"title":["Genetic variation in <i><scp>CD<\/scp>36<\/i>,<i><scp>HBA<\/scp><\/i>,<i><scp>NOS<\/scp>3<\/i> and <i><scp>VCAM<\/scp>1<\/i> is associated with chronic haemolysis level in sickle cell anaemia: a longitudinal study"],"prefix":"10.1111","volume":"92","author":[{"given":"Andreia","family":"Coelho","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Dias","sequence":"additional","affiliation":[{"name":"Departamento de Pediatria Hospital Prof Doutor Fernando Fonseca Amadora Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anabela","family":"Morais","sequence":"additional","affiliation":[{"name":"Departamento de Pediatria Hospital de Santa Maria Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baltazar","family":"Nunes","sequence":"additional","affiliation":[{"name":"Departamento de Epidemiologia INSA Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuel","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Pican\u00e7o","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Faustino","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o","family":"Lavinha","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1353\/hpu.2012.0127"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.07.008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23232"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2006.07.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1993.tb04639.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-870-2_13"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0163"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.5.1555"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21928"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1182\/blood.V82.6.1891.1891","article-title":"Alpha 4 beta 1\u2010integrin expression on sickle reticulocytes: vascular cell adhesion molecule\u20101\u2010dependent binding to endothelium","volume":"82","author":"Swerlick RA","year":"1993","journal-title":"Blood"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.1.268.bloodjournal851268"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20523"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0306"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.3.022502.103149"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.12070"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22274"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.11.028"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.110.004176"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000145359.47708.2f"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22147"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.5.985.985"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12245"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejh.12226","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.12226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T07:28:25Z","timestamp":1695540505000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.12226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,28]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/ejh.12226"],"URL":"https:\/\/doi.org\/10.1111\/ejh.12226","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,28]]}}}