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Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a south Indian population.

ABSTRACT: BACKGROUND:The rupture of a brain aneurysm causes bleeding in the subarachnoid space and is known as aneurysmal subarachnoid haemorrhage (aSAH). In our study, we evaluated the association of factor XIII polymorphism and the risk of Aneurysmal subarachnoid haemorrhage (aSAH) in South Indian population. METHODS:The study was performed in 200 subjects with aSAH and 205 healthy control subjects. Genotyping of rs5985(c.103G?>?T (p.Val35Leu)) and rs5982(c.1694C?>?T (p.Pro564Leu)) polymorphism was performed by Taqman® allelic discrimination assay. RESULTS:In our study, Val/Leu genotype frequency was higher in control subjects (18%) compared to aSAH patients (9%).The Val/Leu genotype was associated with lower risk of aSAH (OR?=?0.48, 95%CI?=?0.26-0.88, p?=?0.02). When compared with Val allele, Leu allele was significantly associated with lower risk of aSAH (OR?=?0.55, 95%CI?=?0.32-0.95, p?=?0.03). In subtyping, we found a significant association of Leu/Leu genotype with the Basilar top aneurysm (OR?=?3.59, 95%CI?=?1.11-11.64, p?=?0.03). In c.1694C?>?T (p.Pro565Leu) variant, Pro/Pro Vs Pro/Leu genotype (OR?=?2.06, 95%CI?=?1.10-3.85, p?=?0.02) was significantly associated with higher risk of aSAH. The 564Leu allelic frequency in aSAH patients (36%) was higher when compared with that in healthy controls (30%) in our study. When allele frequency (Pro Vs Leu) was compared, 564Leu allele was found to be significantly associated with higher aSAH risk (OR?=?1.36, 95%CI?=?1.01-1.83, p?=?0.04). (OR?=?1.36, 95%CI?=?1.01-1.83, p?=?0.04). Regarding rs5985 and rs5982, significant association was found in the log-additive model (OR?=?0.57, 95%CI?=?0.33-0.97, p?=?0.034; OR?=?1.32, 95%CI?=?1.00-1.72, p?=?0.043). CONCLUSION:These results suggest that 34Leu allele was a protective factor for lower risk of aSAH whereas 564Leu allele was associated with higher risk of aSAH in South Indian population.

SUBMITTER: Suvatha A

PROVIDER: S-EPMC6126001 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a south Indian population.

Suvatha Arati A Sibin M K MK Bhat Dhananjaya I DI Narasingarao K V L KVL Vazhayil Vikas V Chetan G K GK

BMC medical genetics 20180905 1

<h4>Background</h4>The rupture of a brain aneurysm causes bleeding in the subarachnoid space and is known as aneurysmal subarachnoid haemorrhage (aSAH). In our study, we evaluated the association of factor XIII polymorphism and the risk of Aneurysmal subarachnoid haemorrhage (aSAH) in South Indian population.<h4>Methods</h4>The study was performed in 200 subjects with aSAH and 205 healthy control subjects. Genotyping of rs5985(c.103G > T (p.Val35Leu)) and rs5982(c.1694C > T (p.Pro564Leu)) polymo ...[more]

PMID: 30185149

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Project description:The prognosis of patients with aneurysmal subarachnoid haemorrhage requiring decompressive craniectomy is usually poor. Proper selection and early performing of decompressive craniectomy might improve the patients' outcome. We aimed at developing a risk score for prediction of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. All consecutive aneurysmal subarachnoid haemorrhage cases treated at the University Hospital of Essen between January 2003 and June 2016 (test cohort) and the University Medical Center Freiburg between January 2005 and December 2012 (validation cohort) were eligible for this study. Various parameters collected within 72 h after aneurysmal subarachnoid haemorrhage were evaluated through univariate and multivariate analyses to predict separately primary (PrimDC) and secondary decompressive craniectomy (SecDC). The final analysis included 1376 patients. The constructed risk score included the following parameters: intracerebral ('Parenchymal') haemorrhage (1 point), 'Rapid' vasospasm on angiography (1 point), Early cerebral infarction (1 point), aneurysm Sac > 5 mm (1 point), clipping (' S urgery', 1 point), age U nder 55 years (2 points), Hunt and Hess grade ≥ 4 ('Reduced consciousness', 1 point) and External ventricular drain (1 point). The PRESSURE score (0-9 points) showed high diagnostic accuracy for the prediction of PrimDC and SecDC in the test (area under the curve = 0.842/0.818) and validation cohorts (area under the curve = 0.903/0.823), respectively. 63.7% of the patients scoring ≥6 points required decompressive craniectomy (versus 12% for the PRESSURE < 6 points, P < 0.0001). In the subgroup of the patients with the PRESSURE ≥6 points and absence of dilated/fixed pupils, PrimDC within 24 h after aneurysmal subarachnoid haemorrhage was independently associated with lower risk of unfavourable outcome (modified Rankin Scale >3 at 6 months) than in individuals with later or no decompressive craniectomy (P < 0.0001). Our risk score was successfully validated as reliable predictor of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. The PRESSURE score might present a background for a prospective randomized clinical trial addressing the utility of early prophylactic decompressive craniectomy in aneurysmal subarachnoid haemorrhage.

Project description:BACKGROUND:Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage. METHODS:We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome-defined as a score of 4-5 on the modified Rankin Scale-3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). FINDINGS:1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION:Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. FUNDING:Netherlands Heart Foundation, UK Medical Research Council.

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Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a south Indian population.

Publications

Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a south Indian population.

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