Association of ATP2B1 common variants with asymptomatic intracranial and extracranial large artery stenosis in hypertension patients

ABSTRACT

Background and aims: Genetic factors play an important role in the cervico-cerebral large-artery atherosclerotic stenosis (LAS), and ATP2B1 gene has been associated with the process of atherosclerosis disorders, such as coronary artery disease and arterial stiffness. But there is little information about the relationship between ATP2B1 gene and atherosclerosis in the intracranial arteries. We hereby investigated the association of common variants in ATP2B1 gene with LAS in asymptomatic Chinese hypertension patients. Methods: The stenosis of intracranial and extracranial arteries were evaluated in 899 subjects through computerized tomography angiography from the aortic arch to the skull base. A total of 11 ATP2B1 common variants were genotyped. Multivariate logistic regression was carried out in a dominant model with confounding factors adjusted. Results: rs17249754-A (OR = 0.43, p = 0.0002) and rs1401982-G (OR = 0.47, p = 0.0007) were associated with decreased susceptibility of concurrent extra and intracranial stenosis even after Bonferroni correction. These two minor alleles were also significantly associated with less stenotic arteries and moderate-to-severe stenosis. Conclusion: rs17249754 and rs1401982 were associated with asymptomatic LAS in stroke-free Chinese hypertension patients and might benefit early recognition of LAS patients in clinical practice.

KEYWORDS:

• Large artery stenosis
• concurrent stenosis
• ATP2B1
• atherosclerosis
• asymptomatic stenosis
• hypertension

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Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The project was supported by grants from the National Natural Science Foundation of China (81670213, 81370205 and 81000037), National Key Program for Basic Research (2009CB521905), Shanghai Municipal Health Bureau Foundation (201640243, 20114Y106), and Natural Science Foundation of Minhang District (2014MHZ060). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the article;National Natural Science Foundation of China [81000037,81370205,81670213];