Yanamandra Krishna, Napper Dawn, Pramanik Arun, Bocchini Joseph A, Dhanireddy Ramasubbareddy
Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, USA.
Ophthalmic Genet. 2010 Dec;31(4):173-7. doi: 10.3109/13816810.2010.497528. Epub 2010 Sep 1.
Retinopathy of Prematurity (ROP) is a vasoproliferative disorder affecting preterm infants leading to visual impairment. ROP is more common in Caucasians than African Americans. Very low birth weight infants have immature retinas and are susceptible to ROP. Because of differences in individual responses to the treatment, various genetic factors have been looked into to understand the etiology of ROP. Endothelial nitric oxide (eNO) serves as a vasodilator, relaxes smooth muscle, prevents platelet aggregation, and facilitates improved blood flow and vascular tonicity. Mutant eNO synthase (eNOS) genotypes result in reduced nitric oxide levels by decreasing enzyme activity. Since eNO affects vasculature and ROP is a vascular disease, the present investigation was aimed at studying the association of genotypes with ROP.
Two eNOS gene single nucleotide polymorphisms (SNPs) (T-786C, and G894T) were studied by microplate-Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP PCR) method. Genotypes were studied in 146 premature infants.
The present data showed significant differences in the baseline gene frequencies between Caucasians and African Americans. ROP patients displayed 3-fold higher frequencies of mutant -786C and 894T alleles in both ethnicities compared to respective controls.
The present data suggest ethnic stratification of genotypes. Mutant -786C and 894T alleles are significant risk factors in the development of ROP, and suggest a strong association between eNOS polymorphisms and the disease. It is interesting to know if a larger dataset of ROP patients can confirm our initial findings.
早产儿视网膜病变（ROP）是一种影响早产儿的血管增殖性疾病，可导致视力损害。ROP在白种人中比非裔美国人更常见。极低出生体重儿的视网膜不成熟，易患ROP。由于个体对治疗的反应存在差异，人们对各种遗传因素进行了研究，以了解ROP的病因。内皮型一氧化氮（eNO）作为一种血管舒张剂，可使平滑肌松弛，防止血小板聚集，并促进改善血流和血管张力。突变型eNO合酶（eNOS）基因型通过降低酶活性导致一氧化氮水平降低。由于eNO影响脉管系统，而ROP是一种血管疾病，因此本研究旨在探讨基因型与ROP的关联。
采用微孔板-限制性片段长度多态性聚合酶链反应（RFLP PCR）方法研究了两个eNOS基因单核苷酸多态性（SNP）（T-786C和G894T）。对146例早产儿的基因型进行了研究。
目前的数据显示，白种人和非裔美国人之间的基线基因频率存在显著差异。与各自的对照组相比，ROP患者在两个种族中突变型-786C和894T等位基因的频率均高出3倍。
目前的数据表明基因型存在种族分层。突变型-786C和894T等位基因是ROP发生的重要危险因素，并表明eNOS多态性与该疾病之间存在密切关联。了解更大样本量的ROP患者数据集是否能证实我们的初步发现很有意思。
