***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND PURPOSE Factor V Leiden and a prothrombin gene variant , G20210A , are mutations associated with a thrombotic risk . The aim of our study was to assess whether these mutations increase the risk of stroke in women under 45 years of age . METHODS We conducted a case-control study in western Washington state . Case patients were women aged 18 to 44 years with a first stroke ( n = 106 ) . Control subjects were women without stroke recruited from the same region by use of r and om-digit telephone dialing ( n = 391 ) . All were interviewed and provided blood specimens , which were genotyped for these mutations . RESULTS Factor V Leiden was found in 0.9 % of case patients , a single patient with a subarachnoid hemorrhage , and in 4.1 % of control subjects . The odds ratio ( OR ) for any stroke was 0.2 ( 95 % confidence interval [ CI ] , 0.03 to 1.7 ) . The prothrombin variant was found in 1.9 % of case patients , 1 with a venous stroke and 1 with an ischemic stroke , and in 1.6 % of control subjects . The OR for any stroke was 1.48 ( 95 % CI , 0.14 to 9.17 ) . ORs for stroke types were also not statistically significant . CONCLUSIONS In this study , neither factor V Leiden nor the prothrombin variant ( G20210A ) was an important risk factor for stroke in young women . In this setting , screening for these mutations can not be recommended . Unanswered by this study is whether screening would be useful in select patients , such as those with a strong family history of thrombophilia or those with venous strokes Background —The outcome of cardiac surgery is influenced by several factors , but the impact of specific genetic variants has not been systematic ally explored . Because blood conservation is a pressing issue in cardiac surgery , we tested the hypothesis that factor V Leiden ( FVL ) , a common coagulation factor polymorphism , may protect against blood loss and transfusion in patients undergoing cardiac surgery . Methods and Results —We enrolled 517 patients undergoing cardiac surgery , including 26 heterozygous FVL carriers , and evaluated the impact of  FVL on chest tube output and transfusion by using univariate and multivariate techniques . For patients with FVL  , blood loss at 6 ( 238±131 mL ) and 24 hours ( 522±302 mL ) was significantly lower than that for noncarriers ( 358±259 mL and 730±452 mL;P < 0.001 and P = 0.001 , respectively ) . In a multivariate regression analysis , controlling for ethnicity and factors known to affect blood loss , FVL was a significant independent contributor at both time points . Using a similar regression approach , FVL did not have a significant effect on the number of units transfused . However , logistic regression of the risk of receiving any transfusion during hospitalization demonstrated a significant independent protective effect of FVL on overall transfusion risk . Conclusions —FVL represents a common genetic trait that may protect against blood loss and transfusion in this population . This study demonstrates that genetic variability can affect the outcome of cardiac surgery Background and Purpose — Conflicting reports in the literature exist with regard to the association of apolipoprotein E ( apo E ) alleles and  lobar intracerebral hemorrhage ( ICH ) .  We genotyped 12 single-nucleotide polymorphisms in the 5′ upstream regulatory , exonic , and intronic regions of the apo E gene and performed genotype and haplotype association analyses . Methods — We prospect ively enrolled subjects with hemorrhagic stroke and matched them with 2 controls based on age , race , and sex . Each case was review ed by a physician to determine case status and location of the ICH . Multivariate logistic-regression modeling with backward elimination was used to determine significant risk factors for lobar ICH . Associations at the genotype and haplotype levels and linkage disequilibrium were conducted according to st and ard statistical methods . Results — Between May 1997 and December 2002 , 315 cases of ICH were recruited , of whom 107 were lobar ICH cases matched to 205 controls . No association was found for apo E2 , E3 , or E4 with nonlobar ICH . Independent , significant risk factors for lobar ICH included apo E4 , untreated hypertension , anticoagulant use , a first-degree relative with ICH , and ≤high school education ( compared with > high school education ) . Treated hypercholesterolemia compared with “ no history of hypercholesterolemia ” was associated with a decreased risk of lobar ICH . Haplotype association analysis demonstrated a significant association of the apo E gene with lobar ICH among whites ( P<0.0001 ) and blacks ( P=0.0024 ) . Conclusions — Apo E4 is independently associated with lobar ICH but not nonlobar ICH . Haplotypes of the apo E gene are associated with lobar ICH . Untreated hypertension is a risk factor for lobar ICH Intracerebral hemorrhage ( ICH ) is a common and serious type of stroke . Recent studies have shown that inherited factors that affect the devlopment of the vessel wall can increase the risk of ICH . We studied endoglin as a c and i date gene in patients with sporadic ICH , since mutations in this gene can cause telangiectasia formation . One hundred three patients with sporadic ICH and 202 controls were studied . The polymerase chain reaction and single‐str and conformational polymorphism analysis were used to screen for mutations in exon 7 of the endoglin gene . No coding mutations in exon 7 were identified in the ICH patients or controls . A 6‐base intronic insertion was found 26 bases beyond the 3′ end of exon 7 . The homozygous form of the insertion was present in 9 of 103 ( 8.7 % ) ICH patients compared with 4 of 202 ( 2.0 % ) controls , p = 0.012 ( odds ratio 4.8 [ 95 % confidence interval , 1.28 , 21.60 ] ) . Analysis of the endoglin transcript around the insertion did not reveal any changes in the RNA sequence . There were no obvious clinical features that distinguished the ICH patients with the homozygous insertion from the other patients . The pathophysiologic mechanism underlying this association remains to be determined The homozygous deletion allele of the angiotensin converting enzyme gene ( ACE/DD ) , homozygous threonine allele of the angiotensinogen gene ( AGN/TT ) , and the epsilon4 allele of the apolipoprotein E gene ( apoE/epsilon4 ) are reported to be associated with ischemic heart disease . Cerebrovascular disease ( CVD ) is another atherosclerotic disease ; and the effects of these polymorphisms on CVD have been confusing . In this study , we investigated whether ACE/DD , AGN/TT , and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another . We ascertained these genotypes in patients with cerebral infa rct ion ( n = 55 ) and cerebral hemorrhage ( n = 38 ) , diagnosed by brain computed tomography . Control subjects for the infa rct ion group and the hemorrhage group were r and omly selected from 583 subjects matched for age , gender , and history of hypertension with patients . Frequency of ACE/DD genotype was higher in the patients with infa rct ion than in the controls ( chi2 = 6.1 , P < .05 ) . The AGN/TT genotype was not associated with either infa rct ion or hemorrhage , but it increased the relative risk for cerebral infa rct ion in the subjects with ACE/DD genotype ( chi2 = 8.0 , P < .01 , odds ratio ; 11.7 , 95 % confidence intervals : 1.4 to 96.0 ) . There was no significant association between apoE/epsilon4 and CVD . These results suggest that ACE/DD predicts cerebral infa rct ion , but not cerebral hemorrhage , and that AGN/TT enhances the risk for cerebral infa rct ion associated with ACE/DD To determine the prevalence of the factor V Leiden gene mutation in relation to the phenotypes of cerebral infa rct ion and cerebral hemorrhage , we studied 386 r and omly selected cases of acute stroke and 247 control subjects . Factor V genotype was determined by amplification of a 267-bp sequence of exon/intron 10 of the factor V gene . Levels of prothrombin fragment F(1 + 2 ) , a marker of thrombin generation , were determined in both acute and convalescent stroke and related to factor V genotype . Prothrombin fragment F(1 + 2 ) was assessed by using an enzyme-linked immunosorbent assay . Sixteen stroke cases ( 4.1 % ) were identified as having the mutation compared with 14 ( 5.6 % ) control subjects . Prothrombin fragment F(1 + 2 ) levels were estimated in 191 cases and found to be elevated both acutely and after 3 months , but they were not related to factor V genotype . Prothrombin fragment F(1 + 2 ) is elevated in acute stroke and requires further evaluation in relation to cerebrovascular disease . These results suggest that the factor V Leiden gene mutation is not a risk factor for arterial thrombosis causing stroke Abstract The ɛ4 allele of apolipoprotein E ( apoE ) is found more commonly among patients with Alzheimer ’s disease ( AD ) than in the normal population . ApoE is associated with brain amyloid , a component of cerebral amyloid angiopathy ( CAA ) , which is both a pathological feature of AD and a frequent cause of lobar intracerebral hemorrhage ( ICH ) . We hypothesized that the frequency of ɛ4 allele is higher in patients with CAA-related ICH than in hypertensive ICH and in the normal population . To test this hypothesis we compared the frequency of apoE alleles in four population s : 24 patients with lobar ICH , 24 matched patients with hypertensive ICH , 24 matched normal controls , and 173 population controls . Although there was a tendency to a higher frequency of apoE  ɛ4 in lobar ICH patients , we found no significant differences in the frequency of this allele between the four studied population s. In addition we did not confirm the finding of some authors of a higher frequency of apoE ɛ2 in patients with lobar ICH than in the normal population . Previous studies on the subject are discussed . The relationship between apoE polymorphism and lobar CAA-related ICH remains to be clearly defined OBJECT The identification of polymorphisms associated with an increase in the risk of developing disease is integral to the development of genetic biomarkers to identify individuals at risk . Based on reports indicating a role for angiotensin-converting enzyme ( ACE ) in the pathogenesis of intracranial aneurysms ( IAs ) as well as hypertension , an independent risk factor for IAs , the authors investigated the association between an insertion/deletion ( I/D ) polymorphism in the ACE gene and IAs in a Caucasian population in the US . METHODS The patient population consisted of 162 r and omly selected Caucasian patients who underwent surgical repair of an IA at Memorial-Hermann Hospital ( Houston , TX ) and had no family history of the disease . The ACE I/D polymorphism was typed using polymerase chain reaction amplification of genomic DNA , and allele and genotype frequencies were compared between the patients with IAs and 143 healthy Caucasian volunteers ( control group ) by performing logistic regression and chi-square tests . The ACE I/D allele frequencies did not differ significantly between the patient and control population s. There were similar allele and genotype frequencies in male and female study participants in both patient and control population s. The authors found no evidence of an association between the allelic or genotypic distribution of the ACE I/D polymorphism and aneurysmal subarachnoid hemorrhage or unruptured IAs . CONCLUSIONS Contrary to findings in two European Caucasian population s ( one British and one Polish ) , this polymorphism did not contribute to the risk of developing IAs in a Caucasian population in the US Networks of investigators have begun sharing best practice s , tools and methods for analysis of associations between genetic variation and common diseases . A Network of Investigator Networks has been set up to drive the process , sponsored by the Human Genome Epidemiology Network . A workshop is planned to develop consensus guidelines for reporting results of genetic association studies . Published literature data bases will be integrated , and unpublished data , including ' negative ' studies , will be captured by online journals and through investigator networks . Systematic review s will be exp and ed to include more meta-analyses of individual-level data and prospect i ve meta-analyses . Field synopses will offer regularly up date d overviews The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established . Elevated circulating levels of plasminogen activator inhibitor-1 , the principle inactivator of the fibrinolytic system , have been related to the development of myocardial infa rct ion . There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels . We studied a common single nucleotide insertion/deletion ( 4G/5 G ) polymorphism by PCR in 558 patients with stroke , the pathological type of which was established by cranial computed tomography , and in 172 controls . 4G/5 G genotype and PAI-1 activity were investigated in relation to 1 ) stroke type and 2 ) mortality occurring within four weeks , three months and six 
    Output:
    
Our data suggests a genetic contribution to some types of haemorrhagic stroke , with no overall responsible single gene but rather supporting a polygenic aetiology .
Importantly , for several alleles previously found to be associated with protection from ischaemic stroke , there was a trend towards an increased risk of haemorrhagic stroke