Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
J Investig Med. 2009 Oct;57(7):769-76. doi: 10.2310/JIM.0b013e3181b91bbd.
Nitric oxide (NO) is the major mediator in the regulation of vascular homeostasis. It is synthesized by endothelium from arginine with the catalytic help of endothelial NO synthase (eNOS). Polymorphisms in the eNOS gene have been associated inconsistently with many vascular diseases. Conflicting results may arise from ethnic variations, notably in control-case studies. Therefore, to obtain reliable information and improve the design of such genetic association studies, we examined the distribution of genetic alleles of 3 clinically relevant eNOS polymorphisms (the variable number of tandem 27-base pair [bp] repeats in intron 4, T-786C in promoter, and G894T in exon 7) in 300 healthy Turkish individuals with a mean age of 50.07 (SD 12.15) years (range, 22-78 years; 50.7% men and 49.3% women). The haplotype frequency was estimated and associations between 3 polymorphisms were evaluated. We discussed the similarity and differences in the distribution of alleles with other populations. The allele frequencies were 45.3%, 48%, and 62.7% for GG of exon 7, TT of promoter, and bb of intron 4 (wild types), respectively. The most common haplotype combines the wild-type alleles (G-T-b) for all 3 polymorphisms (estimated frequency, 37.6%). The linkage analysis between each pairwise combination showed specific associations between T-786C polymorphism in promotor and G894T polymorphism in exon 7 (positive D' value, +0.3387). No significant correlation was found in the genotype distribution of the 3 polymorphisms with age, sex, and obesity. Our eNOS gene allele distributions resemble those of Caucasians and white populations. Our data showed ethnic differences with other populations in the allele distribution of eNOS gene besides conserved distribution of these polymorphisms in Turkish population. This study produced a reference control data for the 3 eNOS polymorphisms in Turkish population and will be helpful in planning eNOS association studies in vascular disease.
一氧化氮（NO）是血管稳态调节的主要介质。它是由内皮细胞从精氨酸中合成的，其催化作用需要内皮型一氧化氮合酶（eNOS）的帮助。eNOS 基因的多态性与许多血管疾病不一致。冲突的结果可能源于种族差异，特别是在对照病例研究中。因此，为了获得可靠的信息并改进此类遗传关联研究的设计，我们在 300 名健康土耳其个体中检查了 3 种临床相关 eNOS 多态性（内含子 4 中的串联 27 个碱基对[bp]重复数的变量，启动子中的 T-786C 和外显子 7 中的 G894T）的遗传等位基因分布，平均年龄为 50.07（SD 12.15）岁（范围为 22-78 岁；50.7%为男性，49.3%为女性）。估计了单倍型频率，并评估了 3 种多态性之间的关联。我们讨论了与其他人群等位基因分布的相似性和差异。外显子 7 的 GG、启动子的 TT 和内含子 4 的 bb（野生型）的等位基因频率分别为 45.3%、48%和 62.7%。最常见的单倍型结合了所有 3 种多态性的野生型等位基因（G-T-b）（估计频率为 37.6%）。每个成对组合之间的连锁分析显示，启动子中的 T-786C 多态性和外显子 7 中的 G894T 多态性之间存在特定关联（阳性 D' 值，+0.3387）。在 3 种多态性的基因型分布与年龄、性别和肥胖之间未发现显著相关性。我们的 eNOS 基因等位基因分布与白种人和高加索人相似。除了土耳其人群中这些多态性的保守分布外，我们的研究还表明，eNOS 基因的等位基因分布在其他人群中存在种族差异。本研究为土耳其人群中 eNOS 基因的 3 种多态性提供了参考对照数据，并将有助于计划血管疾病中 eNOS 关联研究。
