Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke

Objective: Cystatin C, a marker of atherosclerosis, is encoded by CST3. We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of CST3 are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis. Methods: This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of CST3 were selected based on the strong association with cystatin C concentration. Results: Two loci of CST3 (rs13038305 and rs911119) were analyzed in 3,833 ischemic stroke patients. Carriers of T allele in rs13038305 and C allele in rs911119 tend to have lower serum cystatin C levels (p < 0.05). Compared with C/C as a reference in rs13038305, odds ratio (OR) of T/T was 0.486, 95% CI 0.237-0.994, p = 0.048. Per C allele of rs13038305 also showed an increased level of low-density lipoprotein cholesterol (LDL-C), β (95% CI) was 1.335 (1.008-1.250), p = 0.044. No correlation was found between the selected SNPs and stroke prognosis (functional outcome, recurrence, and mortality). Conclusions: Carriers of the T allele in rs13038305 tend to have a lower proportion of LAAS. rs13038305 and rs911119 polymorphisms were likely to affect cystatin C concentration independently of kidney function.