Polymorphism in factor VII gene modifies phenotype of severe haemophilia
The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes ma...
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| Veröffentlicht in: | Haemophilia : the official journal of the World Federation of Hemophilia 2009-11, Vol.15 (6), p.1228-1236 |
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| creator | JAYANDHARAN, G. R. NAIR, S. C. POONNOOSE, P. M. THOMAS, R. JOHN, J. KESHAV, S. K. CHERIAN, R. S. DEVADARISHINI, M. LAKSHMI, K. M. SHAJI, R. V. VISWABANDYA, A. GEORGE, B. MATHEWS, V. CHANDY, M. SRIVASTAVA, A. |
| description | The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as ‘mild’ ( |
| doi_str_mv | 10.1111/j.1365-2516.2009.02080.x |
| format | Article |
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R. ; NAIR, S. C. ; POONNOOSE, P. M. ; THOMAS, R. ; JOHN, J. ; KESHAV, S. K. ; CHERIAN, R. S. ; DEVADARISHINI, M. ; LAKSHMI, K. M. ; SHAJI, R. V. ; VISWABANDYA, A. ; GEORGE, B. ; MATHEWS, V. ; CHANDY, M. ; SRIVASTAVA, A.</creator><creatorcontrib>JAYANDHARAN, G. R. ; NAIR, S. C. ; POONNOOSE, P. M. ; THOMAS, R. ; JOHN, J. ; KESHAV, S. K. ; CHERIAN, R. S. ; DEVADARISHINI, M. ; LAKSHMI, K. M. ; SHAJI, R. V. ; VISWABANDYA, A. ; GEORGE, B. ; MATHEWS, V. ; CHANDY, M. ; SRIVASTAVA, A.</creatorcontrib><description>The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as ‘mild’ (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or ‘severe’ (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P ≤ 0.001) and life‐time clotting factor use (P ≤ 0.007) were different. Patients with severe molecular defects had a 4.1‐fold increased risk for a severe phenotype (95% CI: 1.18–14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04–12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.</description><identifier>ISSN: 1351-8216</identifier><identifier>EISSN: 1365-2516</identifier><identifier>DOI: 10.1111/j.1365-2516.2009.02080.x</identifier><identifier>PMID: 19686262</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Biomarkers ; Blood Coagulation Factors - genetics ; Child ; Child, Preschool ; Factor VII - genetics ; Genetic Association Studies ; Genotype ; haemophilia ; Hemophilia A - genetics ; Hemophilia B - genetics ; Hemorrhage - etiology ; Hemorrhage - genetics ; Humans ; Male ; Middle Aged ; Phenotype ; polymorphism ; Polymorphism, Genetic - genetics ; Severity of Illness Index ; variation ; Young Adult</subject><ispartof>Haemophilia : the official journal of the World Federation of Hemophilia, 2009-11, Vol.15 (6), p.1228-1236</ispartof><rights>2009 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4370-25884883596c1230d3a71dffe3bdfdf7ddc4b410a67e55ae1f072a88c9dbda3b3</citedby><cites>FETCH-LOGICAL-c4370-25884883596c1230d3a71dffe3bdfdf7ddc4b410a67e55ae1f072a88c9dbda3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2516.2009.02080.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2516.2009.02080.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19686262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JAYANDHARAN, G. R.</creatorcontrib><creatorcontrib>NAIR, S. C.</creatorcontrib><creatorcontrib>POONNOOSE, P. M.</creatorcontrib><creatorcontrib>THOMAS, R.</creatorcontrib><creatorcontrib>JOHN, J.</creatorcontrib><creatorcontrib>KESHAV, S. K.</creatorcontrib><creatorcontrib>CHERIAN, R. S.</creatorcontrib><creatorcontrib>DEVADARISHINI, M.</creatorcontrib><creatorcontrib>LAKSHMI, K. M.</creatorcontrib><creatorcontrib>SHAJI, R. V.</creatorcontrib><creatorcontrib>VISWABANDYA, A.</creatorcontrib><creatorcontrib>GEORGE, B.</creatorcontrib><creatorcontrib>MATHEWS, V.</creatorcontrib><creatorcontrib>CHANDY, M.</creatorcontrib><creatorcontrib>SRIVASTAVA, A.</creatorcontrib><title>Polymorphism in factor VII gene modifies phenotype of severe haemophilia</title><title>Haemophilia : the official journal of the World Federation of Hemophilia</title><addtitle>Haemophilia</addtitle><description>The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as ‘mild’ (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or ‘severe’ (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P ≤ 0.001) and life‐time clotting factor use (P ≤ 0.007) were different. Patients with severe molecular defects had a 4.1‐fold increased risk for a severe phenotype (95% CI: 1.18–14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04–12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biomarkers</subject><subject>Blood Coagulation Factors - genetics</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Factor VII - genetics</subject><subject>Genetic Association Studies</subject><subject>Genotype</subject><subject>haemophilia</subject><subject>Hemophilia A - genetics</subject><subject>Hemophilia B - genetics</subject><subject>Hemorrhage - etiology</subject><subject>Hemorrhage - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Severity of Illness Index</subject><subject>variation</subject><subject>Young Adult</subject><issn>1351-8216</issn><issn>1365-2516</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v0zAYgC0EYmPwF5BPcErwR_yRA4dp2tZKGwPGh8TFcuLX1CWpM7uF9t-TrNV2Q_hiS36e19aDEKakpON6tywpl6JggsqSEVKXhBFNyu0TdPxw8XQ6C1poRuURepHzkhDKGZHP0RGtpZZMsmM0-xi7XR_TsAi5x2GFvW3XMeFv8zn-CSvAfXTBB8h4WMAqrncD4Ohxht-QAC8s9HFUu2BfomfedhleHfYT9PXi_MvZrLi6uZyfnV4VbcUVGX-mdaU1F7VsKePEcauo8x5447zzyrm2aipKrFQghAXqiWJW67Z2jbO84Sfo7X7ukOLdBvLa9CG30HV2BXGTjeIV41TW1Ui--SfJKBW1FmQE9R5sU8w5gTdDCr1NO0OJmXqbpZmymimrmXqb-95mO6qvD29smh7co3gIPALv98Cf0MHuvweb2en5dBr9Yu-HvIbtg2_TLyMVV8J8_3Bpfny6Jerz9a254H8BWG2dpw</recordid><startdate>200911</startdate><enddate>200911</enddate><creator>JAYANDHARAN, G. R.</creator><creator>NAIR, S. C.</creator><creator>POONNOOSE, P. M.</creator><creator>THOMAS, R.</creator><creator>JOHN, J.</creator><creator>KESHAV, S. K.</creator><creator>CHERIAN, R. S.</creator><creator>DEVADARISHINI, M.</creator><creator>LAKSHMI, K. M.</creator><creator>SHAJI, R. V.</creator><creator>VISWABANDYA, A.</creator><creator>GEORGE, B.</creator><creator>MATHEWS, V.</creator><creator>CHANDY, M.</creator><creator>SRIVASTAVA, A.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200911</creationdate><title>Polymorphism in factor VII gene modifies phenotype of severe haemophilia</title><author>JAYANDHARAN, G. R. ; NAIR, S. C. ; POONNOOSE, P. M. ; THOMAS, R. ; JOHN, J. ; KESHAV, S. K. ; CHERIAN, R. S. ; DEVADARISHINI, M. ; LAKSHMI, K. M. ; SHAJI, R. 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R.</au><au>NAIR, S. C.</au><au>POONNOOSE, P. M.</au><au>THOMAS, R.</au><au>JOHN, J.</au><au>KESHAV, S. K.</au><au>CHERIAN, R. S.</au><au>DEVADARISHINI, M.</au><au>LAKSHMI, K. M.</au><au>SHAJI, R. V.</au><au>VISWABANDYA, A.</au><au>GEORGE, B.</au><au>MATHEWS, V.</au><au>CHANDY, M.</au><au>SRIVASTAVA, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphism in factor VII gene modifies phenotype of severe haemophilia</atitle><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle><addtitle>Haemophilia</addtitle><date>2009-11</date><risdate>2009</risdate><volume>15</volume><issue>6</issue><spage>1228</spage><epage>1236</epage><pages>1228-1236</pages><issn>1351-8216</issn><eissn>1365-2516</eissn><abstract>The basis for 10–15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as ‘mild’ (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or ‘severe’ (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P ≤ 0.001) and life‐time clotting factor use (P ≤ 0.007) were different. Patients with severe molecular defects had a 4.1‐fold increased risk for a severe phenotype (95% CI: 1.18–14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04–12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19686262</pmid><doi>10.1111/j.1365-2516.2009.02080.x</doi><tpages>9</tpages></addata></record> |
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| subjects | Adolescent Adult Biomarkers Blood Coagulation Factors - genetics Child Child, Preschool Factor VII - genetics Genetic Association Studies Genotype haemophilia Hemophilia A - genetics Hemophilia B - genetics Hemorrhage - etiology Hemorrhage - genetics Humans Male Middle Aged Phenotype polymorphism Polymorphism, Genetic - genetics Severity of Illness Index variation Young Adult |
| title | Polymorphism in factor VII gene modifies phenotype of severe haemophilia |
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