内皮型一氧化氮合酶基因多态性与原发性高血压、2型糖尿病的关系

目的：探讨内皮型一氧化氮合酶（eNOS)基因27bp数目可变的串联重复序列（VNTR）多态性与中国汉族人原发性高血压（EH），2型糖尿病（DM)关系。方法：（1）聚合酶链反应（PCR）－琼脂糖凝胶电泳检测基因型。（2）硝酸盐还原酶法测定空腹血清一氧化氮代谢物（NOx)水平。（3）放免法检测葡萄糖耐量试验时血清免疫活性胰岛素（IRI），C肽（CP)。结果：（1）EH组，2型DM组a等位基因频率显著高于对照组（0．109和0．051；0．129对0．051，P均＜0．05）。2型DM组aa ab基因型频率显著高于对照组（0．224对0．103，P＜0．05）。（2）对照组内aa ab基因型空腹血清NOx明显低于bb基因型（P＜0．05）。（3）EH组aa ab基因型空腹，糖负荷后血清IRI，CP均高于bb基因型，其中部分时点差异有显著性（P＜0．01或P＜0．05）。2型DM组aa ab基因型间各个点血清IRI，CP变化方向不一致。（4）EH组内aa ab基因型HOMA－IR显著高于bb基因组（P＜0．05）。结论：eNOS 基因27bpVNTR多态性与中国汉族人EH及2型DM发生有关,a等位基因可能通过减少内皮基础NO释放参与EH发病，通过胰岛素抵抗机制参与EH和2型DM的发病。

Associaton of polymorphism of endothelial nitric oxide synthase gene with essential hypertension and type 2 diabetes mellitus

Objective To investigate the association of the polymorphism of endothelial nitric oxide synthase (eNOS) gene 27bp variable number of tandem repeats (VNTR) with essential hypertension (EH) and type 2 diabetes mellitus (DM) in Chinese population. Methods (1) Genotypes were determined by polymerase chain reaction (PCR)-agarose gel electrophoresis. (2) Fasting serum nitric oxide metabolites (NOx) were measured by nitrate reductase. (3) During oral glucose tolerance test (OGTT) serum immunoreactive insulin (IRI) and C peptide (CP) were measured by radioimmunoassay. Results (1) The frequenciesofaalleleinEHandtype2DMgroupwere significantly higher than that in control group (0.109 vs 0.051; 0.129vs 0.051, P<0.05). The frequency of aa+ab genotype in type 2 DM group was significantly higher than that in control group (0.224 vs 0.103, P<0.05). (2) Fasting serum NOx in aa+ab genotype was significantly lower than that in bb genotype of control group (P<0.05). (3) In EH group, serum IRI and CP during OGTT in aa+ab genotype were all higher than those in bb genotype. Among them, serum IRI and CP at fasting, 30 min, 180 min and serum CP at 120 min showed significant differences between aa+ab and bb genotypes (P<0.01 or P<0.05). Whereas in type 2 DM group, serum IRI and serum CP at 30 min, 60 min in aa+ab genotypes during OGTT were higher than those in bb genotype, only serum IRI at 30 min, 60 min and serum CP at 60 min showed significant differences between aa+ab and bb genotypes (P<0.01 or P<0.05). (4) The HOMA-IR of aa+ab genotype was significantly higher than that of bb genotype in EH group (P<0.05). Conclusion The polymorphism of eNOS gene 27bp VNTR is associated with EH and type 2 DM in Chinese population. It is suggested that a allele may be involved in the etiology of EH by reducing basal NO release of endothelium and also involved in the etiology of EH and type 2 DM by insulin resistance.