Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.
Acta Diabetol. 2023 Jun;60(6):749-756. doi: 10.1007/s00592-023-02059-2. Epub 2023 Mar 1.
Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD.
This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts).
SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74-83], 75 [70-80], and 75 [72-81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy.
Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
脑小血管病(SVD)在 1 型糖尿病中很常见,与结合珠蛋白变异等位基因 Hp1 有关。相反,Hp2 等位基因与心血管疾病有关,结合珠蛋白基因型在无症状 SVD 中的作用尚不清楚。因此,我们旨在评估等位基因与 SVD 的关联。
本横断面研究纳入了 179 名神经无症状的 1 型糖尿病成人(女性 53%,平均年龄 39±7 岁,糖尿病病程 23±10 年,HbA1c8.1±3.2%[65±12mmol/mol])。通过聚合酶链反应进行基因型(基因型 Hp1-1、Hp2-1、Hp2-2)检测,进行临床调查,并进行磁共振脑成像评估 SVD 表现(脑白质高信号、脑微出血和腔隙性梗死)。
SVD 患病率为 34.6%。结合珠蛋白基因型频率分别为 15.6%(Hp1-1)、43.6%(Hp1-2)和 40.8%(Hp2-2)。只有舒张压在 Hp1-1、Hp1-2 和 Hp2-2 基因型之间存在差异(81[74-83]、75[70-80]和 75[72-81]mmHg,p=0.019)。有 SVD 与无 SVD 患者的结合珠蛋白基因型频率分别为 16.1%、46.8%、37.1%和 15.4%、41.9%、42.7%(p=0.758)。次要等位基因频率分别为 39.5%和 36.3%(p=0.553)。Hp1 纯合子和 Hp2 携带者的 SVD 比例相等(35.7%与 34.4%,p>0.999)和 SVD 表现(脑白质高信号 14.3%与 17.9%,p=0.790;微出血 25.0%与 21.9%,p=0.904;腔隙性梗死 0%与 3.6%,p>0.999)。调整年龄、血压和糖尿病视网膜病变后,Hp1-1 与 SVD 无显著相关性(OR 1.19,95%CI 0.46-2.94,p=0.712)。
尽管 SVD 的患病率较高,但我们未发现 SVD 与结合珠蛋白基因型之间存在显著关联。