Association between Ngb polymorphisms and ischemic stroke in the Southern Chinese Han population.
BACKGROUND
Neuroglobin (Ngb), one of novel members of the globin superfamily, is expressed predominantly in brain neurons, and appears to modulate hypoxic-ischemic insults. The mechanisms underlying Ngb-mediated neuronal protection are still unclear. For it is one of the candidate protective factors for ischemic stroke, we conducted a case-control study to clarify the association of Ngb polymorphisms with ischemic stroke in the Southern Chinese Han population.


METHODS
355 cases and 158 controls were recruited. With brain imaging, cases were subdivided into large-artery atherosclerosis (LVD) and small-vessel occlusion (SVD) stroke. PCR amplified all the four exons of Ngb and flanking intron sequence for each exon. Genotyping for Ngb was achieved by direct sequencing and mismatched PCR-RFLP. Polymorphisms were studied both individually and as haplotypes in each group and subgroup which subdivided according to gender or age.


RESULTS
Two intronic polymorphisms 89+104 c>t and 322-110 (6a)>5a were identified. The allele frequency of 89+104 t was decreased in stroke cases. The protective effect seems to be more pronounced in subgroups of female patients and age > 60 years. Also, we have confirmed decreased LDL-C level and reduced hypertension and hypercholesterolemia in 89+104 t allele carriers. In contrast, the 322-110 (6a)>5a genotype distribution was similar between cases and controls. However, the haplotype 89+104 c>t/322-110 (6a)>5a was related with LVD and SVD stroke. The haplotype c-5a was more frequent in both LVD and SVD groups while t-6a was more frequent in controls.


CONCLUSIONS
Ngb polymorphism 89+104 t had protective effects on LVD and SVD in the Southern Chinese Han population. A "hitchhiking" effect was observed for the 89+104 t/322-110 (6a) genotype combination especially for LVD.
Lin
Yi
Y
Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China. linyi7811@yahoo.com.cn
Fang
Ling
L
Xue
Xie-Hua
XH
Murong
Shen-Xing
SX
Wang
Ning
N
Wu
Zhi-Ying
ZY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000078787:Neuroglobin; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins