Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan.
BACKGROUND
The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.


METHODS
We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.


RESULTS
There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.


CONCLUSIONS
This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.
School of Public Health, Taipei Medical University, Taipei, Taiwan.
Yi-Chen
YC
Hsieh
Sudha
S
Seshadri
Wen-Ting
WT
Chung
Fang-I
FI
Hsieh
Yi-Hsiang
YH
Hsu
Huey-Juan
HJ
Lin
Hung-Pin
HP
Tseng
Li-Ming
LM
Lien
Chyi-Huey
CH
Bai
Chaur-Jong
CJ
Hu
Jiann-Shing
JS
Jeng
Sung-Chun
SC
Tang
Chin-I
CI
Chen
Chia-Chen
CC
Yu
Hung-Yi
HY
Chiou
D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology