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β-纤维蛋白原基因启动子A -455等位基因与芬兰中风队列中55至71岁白种女性的长期生存率低有关。

Βeta-fibrinogen gene promoter A -455 allele associated with poor longterm survival among 55-71 years old Caucasian women in Finnish stroke cohort.

作者信息

Martiskainen Mika, Oksala Niku, Pohjasvaara Tarja, Kaste Markku, Oksala Anni, Karhunen Pekka J, Erkinjuntti Timo

机构信息

Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.

出版信息

BMC Neurol. 2014 Jun 22;14:137. doi: 10.1186/1471-2377-14-137.

Abstract

BACKGROUND

Women die of stroke more often than men. After menopause, the incidence of ischemic stroke increases rapidly. Elevated fibrinogen levels and smoking have been associated with an increased risk of stroke. In gene-cluster haplotype analyses, the beta-fibrinogen (FGB) promoter -455 G/A polymorphic locus was most strongly associated with elevated plasma fibrinogen levels. We investigated whether the FGB -455 G/A polymorphism and smoking might interact with sex on longterm survival of acute stroke sufferers.

METHODS

The Stroke Aging Memory (SAM) cohort comprising 486 consecutive stroke patients (55-85 years, 246 men, 240 women) subjected to clinical and MRI examination was followed over 12.5 years. During this period 347 (71.4%) patients died. The genotypes of the FGB -455 G/A polymorphism were determined by PCR.

RESULTS

The FGB -455 G/A polymorphism genotype distributions were 64.7%, 32.1%, and 3.2% for GG, GA, and AA, respectively. During the follow-up, the FGB -455 A + genotype did not associate with survival, nor was there any genotype-by-smoking interaction on poor outcome in the total study population. However, women aged 55-71 years who carried the FGB -455 A-allele showed worse survival regardless of smoking status compared to non-smoking FGB -455 GG homozygotes (non-smokers, crude HR = 5.21, 95% CI: 1.38-19.7; smokers, crude HR = 7.03, 95% CI: 1.81-27.3). This association persisted in adjusted analyses. No such association was observed for women in the oldest age-group, nor among men.

CONCLUSION

The A + genotype of the FGB -455 G/A polymorphism associated with poor survival among 55-71 years old Caucasian women in the Finnish stroke cohort.

摘要

背景

女性死于中风的情况比男性更为常见。绝经后,缺血性中风的发病率迅速上升。纤维蛋白原水平升高和吸烟与中风风险增加有关。在基因簇单倍型分析中,β-纤维蛋白原(FGB)启动子-455 G/A多态性位点与血浆纤维蛋白原水平升高关联最为密切。我们研究了FGB -455 G/A多态性和吸烟是否会在急性中风患者的长期生存方面与性别产生相互作用。

方法

对连续纳入的486例接受临床和MRI检查的中风患者(年龄55 - 85岁,男性246例,女性240例)组成的中风衰老记忆(SAM)队列进行了12.5年的随访。在此期间,347例(71.4%)患者死亡。通过聚合酶链反应(PCR)确定FGB -455 G/A多态性的基因型。

结果

FGB -455 G/A多态性的基因型分布中,GG型为64.7%,GA型为32.1%,AA型为3.2%。在随访期间,FGB -455 A +基因型与生存率无关,在整个研究人群中也不存在基因型与吸烟在不良结局方面的相互作用。然而,与不吸烟的FGB -455 GG纯合子相比,携带FGB -455 A等位基因的55 - 71岁女性无论吸烟状况如何,生存率均较差(不吸烟者,粗危险比[HR]=5.21,95%可信区间[CI]:1.38 - 19.7;吸烟者,粗HR = 7.03,95% CI:1.81 - 27.3)。这种关联在调整分析中仍然存在。在最年长年龄组的女性中未观察到这种关联,在男性中也未观察到。

结论

在芬兰中风队列中,FGB -455 G/A多态性的A +基因型与55 - 71岁白种女性的不良生存相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c2/4131463/af2702e2ca4e/1471-2377-14-137-1.jpg

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