Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Diabetes. 2022 Dec 1;71(12):2728-2738. doi: 10.2337/db22-0327.
The exon copy number variant in the haptoglobin gene is associated with cardiovascular and kidney disease. For stroke, previous research is inconclusive. We aimed to study the relationship between the haptoglobin Hp1/2 genotype and stroke in individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study. We included two partially overlapping cohorts: one with haptoglobin genotypes determined using genotyping for 179 individuals with stroke and 517 matched control subjects, and the other using haptoglobin genotype imputation for a larger cohort of 500 individuals with stroke and 3,806 individuals without stroke. We observed no difference in the Hp1-1, Hp2-1, and Hp2-2 genotype frequencies between individuals with or without stroke, neither in the genotyping nor the imputation cohorts. Haptoglobin genotypes were also not associated with the ischemic or hemorrhagic stroke subtypes. In our imputed haptoglobin cohort, 61% of individuals with stroke died during follow-up. However, the risk of death was not related to the haptoglobin genotype. Diabetic kidney disease and cardiovascular events were common in the cohort, but the haptoglobin genotypes were not associated with stroke when stratified by these complications. To conclude, the Hp1/2 genotypes did not affect the risk of stroke or survival after stroke in our cohort with type 1 diabetes.
载脂蛋白基因外显子拷贝数变异与心血管和肾脏疾病有关。对于中风,先前的研究尚无定论。我们旨在研究芬兰糖尿病肾病研究中 1 型糖尿病个体中载脂蛋白 Hp1/2 基因型与中风之间的关系。我们纳入了两个部分重叠的队列:一个队列使用基因分型确定了 179 名中风患者和 517 名匹配对照者的载脂蛋白基因型,另一个队列使用载脂蛋白基因型推断确定了 500 名中风患者和 3806 名无中风患者的载脂蛋白基因型。我们在有或没有中风的个体之间,无论是在基因分型还是推断队列中,都没有观察到 Hp1-1、Hp2-1 和 Hp2-2 基因型频率的差异。载脂蛋白基因型也与缺血性或出血性中风亚型无关。在我们推断的载脂蛋白队列中,61%的中风患者在随访期间死亡。然而,风险的死亡与载脂蛋白基因型无关。该队列中糖尿病肾病和心血管事件很常见,但在分层这些并发症时,载脂蛋白基因型与中风无关。总之,在我们的 1 型糖尿病队列中,Hp1/2 基因型不会影响中风风险或中风后的生存率。