Akoudad Saloua, Ikram M Arfan, Portegies Marileen L P, Adams Hieab H, Bos Daniel, Hofman Albert, Koudstaal Peter J, Uitterlinden Andre G, van der Lugt Aad, van Duijn Cornelia M, Vernooij Meike W
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
Atherosclerosis. 2016 Mar;246:287-92. doi: 10.1016/j.atherosclerosis.2016.01.024. Epub 2016 Jan 18.
Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds.
Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997-2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds.
After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants suffered an ICH. Microbleed prevalence was 19.6%. Higher genetic load for high serum total and LDL cholesterol was associated with an increased risk of ICH. Higher genetic load for high serum LDL cholesterol was borderline associated with a higher prevalence of multiple lobar microbleeds.
Genetic susceptibility for high serum total and LDL cholesterol is positively associated with incident ICH and borderline associated with multiple lobar microbleeds. We did not find a genetic basis for the previously reported inverse association between serum lipid levels and ICH.
血清总胆固醇及其组分与脑出血（ICH）及其潜在的亚临床前驱病变脑微出血呈负相关。为确定这种负相关是否存在遗传基础，我们研究了血清总胆固醇、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）胆固醇以及甘油三酯的既定遗传位点与ICH和脑微出血的关联。
在基于人群的鹿特丹研究中，收集了9011名无卒中参与者（平均年龄65.8岁，标准差10.2；女性占57.9%）的161种血清脂质基因变异数据。参与者从基线（1997 - 2005年）开始随访至2013年，观察ICH的发生情况。2005年至2011年间，4179名参与者的子集接受了脑部MRI检查以评估脑微出血。我们计算了脂质变异联合效应的遗传风险评分（GRS）。采用Cox比例风险模型和逻辑回归模型研究脂质组分GRS与ICH和脑微出血的关联。
平均随访8.7（标准差4.1）年后，67名（0.7%）参与者发生了ICH。脑微出血患病率为19.6%。血清总胆固醇和LDL胆固醇水平高的较高遗传负荷与ICH风险增加相关。血清LDL胆固醇水平高的较高遗传负荷与多叶脑微出血的较高患病率存在临界关联。
血清总胆固醇和LDL胆固醇水平高的遗传易感性与ICH发病呈正相关，与多叶脑微出血存在临界关联。我们未发现先前报道的血清脂质水平与ICH之间负相关的遗传基础。
