Lin Yi, Fang Ling, Xue Xie-Hua, Murong Shen-Xing, Wang Ning, Wu Zhi-Ying
Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China.
BMC Med Genet. 2008 Dec 16;9:110. doi: 10.1186/1471-2350-9-110.
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.
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.
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.
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.
神经球蛋白（Ngb）是珠蛋白超家族的新成员之一，主要在脑神经元中表达，似乎能调节缺氧缺血性损伤。Ngb介导神经元保护的机制仍不清楚。由于它是缺血性中风的候选保护因子之一，我们进行了一项病例对照研究，以阐明中国南方汉族人群中Ngb基因多态性与缺血性中风的关联。
招募了355例病例和158例对照。通过脑成像，将病例分为大动脉粥样硬化（LVD）和小血管闭塞（SVD）性中风。对Ngb的所有四个外显子及其侧翼内含子序列进行PCR扩增。通过直接测序和错配PCR-RFLP对Ngb进行基因分型。在根据性别或年龄划分的每个组和亚组中，分别对多态性及其单倍型进行研究。
鉴定出两个内含子多态性89+104 c>t和322-110（6a）>5a。中风病例中89+104 t的等位基因频率降低。这种保护作用在女性患者亚组和年龄>60岁的人群中似乎更为明显。此外，我们证实89+104 t等位基因携带者的低密度脂蛋白胆固醇（LDL-C）水平降低，高血压和高胆固醇血症减少。相比之下，病例组和对照组之间322-110（6a）>5a的基因型分布相似。然而，单倍型89+104 c>t/322-110（6a）>5a与LVD和SVD中风有关。单倍型c-5a在LVD和SVD组中均更常见，而t-6a在对照组中更常见。
Ngb基因多态性89+104 t对中国南方汉族人群的LVD和SVD具有保护作用。观察到89+104 t/322-110（6a）基因型组合存在“搭便车”效应，尤其是对于LVD。
