{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:57:44Z","timestamp":1778903864439,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aim:<\/jats:title>\n                    <jats:p>Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K antagonist has a narrow therapeutic range and wide inter-individual variability. Our aim was to investigate the influence of polymorphisms of VKORC1 and CYP2C9 genes on the mean daily dose requirement of acenocoumarol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      205 chronic RHD patients, with mechanical heart valves and on acenocoumarol therapy, were recruited. Genotyping for VKORC1 (\u22121639G&gt;A and 1173C&gt;T) and CYP2C9 (*2 &amp; *3 alleles) polymorphisms was done by PCR-RFLP. There was complete linkage disequilibrium between VKORC1 polymorphisms (r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.98, D\u2032 = 1.0, LOD = 74.02). VKORC1 genotype distribution for GG\/CC, GA\/CT, and AA\/TT were 57.6%, 36.1%, and 6.3%, respectively. CYP2C9 genotype distribution for *1\/*1, *1\/*3, *1\/*2, *2\/*2, and *2\/*3 were 78.5%, 14.1%, 6.3%, 0.5%, and 0.5%, respectively. Patients with a wild type of both VKORC1 (\u22121639GG and 1173CC) and CYP2C9 gene variants required higher acenocoumarol dose compared to those with mutant genotype ( P = 0.023 and P = 0.008 respectively). On combined genotype analysis, patients having a combination of wild type of VKORC1 with wild type of CYP2C9 (44.4%) required higher daily dose compared to patients bearing heterozygous VKORC1 (\u22121639GA &amp; 1173CT) with wild type of CYP2C9 (30.2%, P = 0.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Presence of a mutant allele of VKORC1 (\u22121639A &amp; 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1076029616655617","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T21:28:40Z","timestamp":1466630920000},"page":"876-882","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Influence of\n                    <i>VKORC1<\/i>\n                    and\n                    <i>CYP2C9<\/i>\n                    Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves"],"prefix":"10.1177","volume":"23","author":[{"given":"S. R.","family":"Kalpana","sequence":"first","affiliation":[{"name":"Department of Pathology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Bharath","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. N.","family":"Manjunath","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Christopher","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,6,22]]},"reference":[{"issue":"3","key":"bibr1-1076029616655617","first-page":"397","volume":"97","author":"Krishna KR","year":"2009","journal-title":"Curr 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