{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:30Z","timestamp":1759708830069},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,3,22]],"date-time":"2001-03-22T00:00:00Z","timestamp":985219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sickle cell disease (SCD) is relatively mild among Kuwaiti Arabs. However, an atypical subset of patients exists with frequent, severe vaso\u2010occlusive crisis and osteonecrosis. The thermolabile variant of MTHFR, resulting from a C\u2192T mutation at nucleotide 677, has been shown to be associated with hyperhomocysteinemia, which is an important risk factor for premature vascular disease. We have screened an unselected group of 41 Kuwaiti SCD patients (33 SS and 8 S\u03b2<jats:sup>0<\/jats:sup>\u2010thal) attending the Hematology Clinic of Kuwait University Teaching Hospital for the MTHFR mutation, using a PCR\u2010RFLP method. The patients were aged 2\u201341 years (mean of 12.8 \u00b1 8.6). One (2.4%) individual was homozygous for the mutation while 15 (36.6%) were heterozygous, giving an allele frequency of 20.7%. Twenty\u2010one patients (14 SS and 7 S\u03b2<jats:sup>0<\/jats:sup>\u2010thal) were screened for osteonecrosis using MRI of the hip (spin\u2010echo T1\u2010 and T2\u2010weighted images). Seven (33.3%) had varying degrees of osteonecrosis, among whom the frequency of the 677 C\u2192T allele was 21.4%. The frequency was identical among those without osteonecrosis. Although the allele frequency is higher among our patients compared to American SS patients, our results do not suggest an association with osteonecrosis. Am. J. Hematol. 66:263\u2013266, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.1055","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:27:27Z","timestamp":1030310847000},"page":"263-266","source":"Crossref","is-referenced-by-count":22,"title":["Frequency of the 677 C\u2192T mutation of the methylenetetrahydrofolate reductase gene among Kuwaiti sickle cell disease patients"],"prefix":"10.1002","volume":"66","author":[{"given":"A.D.","family":"Adekile","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Kutlar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.Z.","family":"Haider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Kutlar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,3,22]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"202","article-title":"Sickle cell anemia: \u03b2S\u2010globin gene cluster haplotypes as prognostic indicators of vital organ damage","volume":"28","author":"Powars DR","year":"1991","journal-title":"Semin Hematol"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000204216"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000203753"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199609)53:1<1::AID-AJH1>3.0.CO;2-V"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/03630268908998842"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199111213252104"},{"key":"e_1_2_1_8_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00003086-199304000-00018","article-title":"Osteonecrosis of the humeral head in sickle cell disease","volume":"289","author":"Milner PF","year":"1993","journal-title":"Clin Orthop"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199701000-00007"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199104253241701"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_1_12_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1055\/s-0037-1614623","article-title":"Genetic polymorphism of 5,10\u2010MTHFR reductase gene in offspring of patients with coronary infarction","volume":"82","author":"Margaglione M","year":"1999","journal-title":"Thromb Haemostasis"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199809)59:1<46::AID-AJH9>3.0.CO;2-#"},{"issue":"10","key":"e_1_2_1_14_2","first-page":"28b","article-title":"Frequency of a common thermolabile MTHFR (5,10\u2010methylenetetrahydrofolate reductase) mutant among patients with sickle cell disease. 39th Annual Meeting of the American Society for Hematology, San Diego, CA, December 5\u20139, 1997","volume":"90","author":"Kutlar F","year":"1997","journal-title":"Blood"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199812)59:4<267::AID-AJH1>3.0.CO;2-W"},{"issue":"10","key":"e_1_2_1_16_2","first-page":"695a","article-title":"MTHFR (5,10\u2010methylenetetrahydrofolare reductase) 677 C\u2192T mutation as a candidate risk factor for avascular necrosis (AVN) in patients with sickle cell disease","volume":"82","author":"Kutlar F","year":"1998","journal-title":"Blood"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0378-4347(88)80065-3","article-title":"High\u2010performance liquid chromatographic separation of human haemoglobins. 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