KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population.
Stroke is the second most common cause of mortality worldwide, and it is a major cause of physical disability. Several genome-wide association studies have yielded numerous common variants which increase the risk of ischemic stroke, including the Kalirin-coding gene, KALRN. KALRN strongly associates with early-onset coronary artery disease and atherosclerosis and plays an important role in stroke in the European population. In this study, we analyzed four KALRN gene SNPs in 503 ischemic stroke patients and 493 control subjects, separating the patients into separate research groups based on comorbidity with hypertension or diabetes and stroke type (atherosis or lacunar and combination type). We found a rare variant of KALRN, rs11712619, that associated with lacunar stroke in the northern Chinese Han population with an average-risk allele frequency 0.009 (OR 2.95, 95 % CI 1.08-8.01, p = 0.028). However, after adjusting for relevant factors, including sex, age, body mass index, dyslipidemia, alcohol consumption, and smoking, this association was not evident. Additionally, the KALRN variant rs6438833 was associated with ischemic stroke, ischemic stroke comorbid with diabetes, and lacunar stroke after adjusting for the relevant factors (p = 0.046, p = 0.019 and p = 0.046, respectively), which remained significant after 10,000 permutation procedure test (p' = 0.047, p' = 0.018 and p' = 0.048, respectively). The association of these rare and common variants of KALRN with ischemic stroke in northern Chinese Han population offers insight for potential therapeutic research.
Department of Ultrasound, The 2nd Affiliated Hospital of Harbin Medical University, NO. 246, Xuefu Road, Nangang District, Harbin, 150081, Heilongjiang, People's Republic of China.
Meizheng
M
Dang
Zhenzhen
Z
Wang
Ruyou
R
Zhang
Xiaoying
X
Li
Yanqing
Y
Peng
Xuesong
X
Han
Litao
L
Sun
Jiawei
J
Tian
D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D000483:Alleles; D017398:Alternative Splicing; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002545:Brain Ischemia / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D050171:Dyslipidemias / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics* / Q000706:statistics & numerical data; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D059409:Stroke, Lacunar / Q000208:ethnology / Q000235:genetics
D020662:Guanine Nucleotide Exchange Factors; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases