Platelet glycoprotein polymorphisms: risk, in vivo expression and severity of atherothrombotic stroke in Chinese.
BACKGROUND
Polymorphisms in platelet glycoprotein (GP) receptors Ia, Ib and IIIa may be heritable risk factors for platelet-dependent thrombosis leading to death. The precipitation of stroke by occlusive thrombi has led to the investigation of the platelet surface GP receptors, that are involved in critical steps in the activation of platelets. Three polymorphisms in the GP Iba gene and one in each of GPIIIa, GP Ia were selected based on the evidence of functional effects on structure or expression as candidates for risk. We also determined whether these polymorphisms were associated with in vivo expression levels of platelet GP receptors and the severity of the neurological deficit.


METHODS
A Chinese hospital-based case-control study was conducted with 119 cases of atherothrombotic stroke and 166 age and sex matched controls. Genotyping was performed on lymphocyte DNA by standard methods and platelet GP expression levels were measured by flow-cytometry.


RESULTS
Allele and genotype frequencies of the GP receptor polymorphisms differ considerably between ethnic populations. We found the D allele of the GP Iba VNTR polymorphism was significantly associated with atherothrombotic stroke in our Chinese cohort, however we did not find a relationship among these polymorphisms, the expression levels of GP receptors and severity of the neurological deficit.


CONCLUSIONS
In our Chinese cohort the D allele of the GP Iba VNTR polymorphism is associated with atherothrombotic stroke. The number of VNTR repeats alters the length of amino acid sequence, which might affect the structure and function of this receptor.
Zhang
Yong
Y
Department of Neurology, Peking University First Hospital, Beijing, 100034, China. yongzhang_yz@yahoo.com
Wang
Yinhua
Y
Wang
Yunshan
Y
Cui
Caisan
C
Huang
Ping
P
Li
Xianliang
X
Liu
Shuang
S
Lendon
Corinne
C
Guo
Nongjian
N
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D039661:Integrin beta3 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*
D039421:Integrin alpha2; D039661:Integrin beta3; D019038:Platelet Glycoprotein GPIb-IX Complex