Kaur Raminderjit, Singh Jatinder, Kapoor Rohit, Kaur Manpreet
Department of Molecular Biology & Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, India.
Carewell Heart & Superspeciality Hospital, Amritsar, Punjab, India.
Biochem Genet. 2019 Feb;57(1):73-97. doi: 10.1007/s10528-018-9881-6. Epub 2018 Jul 25.
P-selectin, an adhesion molecule, is encoded by SELP and known as biomarker of endothelial as well as platelet dysfunction. SELP polymorphisms (rs6136, rs6127, and rs6125) and raised levels of soluble P-selectin (sP-selectin) have been associated with several disease conditions. The present study was aimed to determine the association of SELP variants and sP-selectin levels as well as vascular risk in Type 2 diabetes mellitus (T2DM) patients. The frequency of rs6136, rs6127, and rs6125 was assessed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). sP-selectin levels were measured using commercially available kits. Haplotypes were constructed using PHASE software. The data obtained from the above-said analyses was subjected to suitable statistical analyses. sP-selectin levels (ng/ml) were significantly higher in patients as compared to controls (p < 0.001). Out of total, 22% of patients were found to have very high vascular risk, 43.2% with high vascular risk, while 34.4% with moderate vascular risk. For both rs6136 and rs6127, frequency of variant allele was found to be significantly higher in patients as compared to controls and accounted for 2.4- and 1.5-fold risk of disease development, respectively. CAG was found to be associated with 4.5-fold risk towards disease development. In contrast, AGG was conferring the protective effect. Significantly high sP-levels were observed in patients with homozygous wild genotype of rs6136, all genotypes of rs6127, and heterozygous genotype of rs6125 as compared to respective controls. Significant difference was observed in P-selectin levels within moderate-risk category for rs6136. When compared between the categories, significant difference was observed for rs6136 and rs6127. Furthermore, patients with haplotypes AAA, AGA, and AGG were found to have significantly high sP-selectin levels as compared to controls. Significant difference in sP-selectin levels was observed within very high-risk as well as high-risk category. When compared between the categories, significant difference was observed for AGA and AGG haplotypes. The studied polymorphisms of SELP have shown significant association with sP-selectin levels as well as vascular risk in T2DM patients.
P-选择素是一种黏附分子，由SELP编码，是内皮功能障碍和血小板功能障碍的生物标志物。SELP基因多态性（rs6136、rs6127和rs6125）以及可溶性P-选择素（sP-选择素）水平升高与多种疾病状况相关。本研究旨在确定SELP基因变异与sP-选择素水平以及2型糖尿病（T2DM）患者血管风险之间的关联。通过限制性片段长度多态性-聚合酶链反应（RFLP-PCR）评估rs6136、rs6127和rs6125的频率。使用市售试剂盒测量sP-选择素水平。使用PHASE软件构建单倍型。对上述分析获得的数据进行适当的统计分析。与对照组相比，患者的sP-选择素水平（ng/ml）显著更高（p < 0.001）。总体而言，发现22%的患者具有非常高的血管风险，43.2%具有高血管风险，而34.4%具有中度血管风险。对于rs6136和rs6127，与对照组相比，患者中变异等位基因的频率显著更高，分别占疾病发生风险的2.4倍和1.5倍。发现CAG与疾病发生风险的4.5倍相关。相比之下，AGG具有保护作用。与各自的对照组相比，在rs6136纯合野生基因型、rs6127的所有基因型以及rs6125杂合基因型的患者中观察到显著高的sP水平。在rs6136的中度风险类别中，P-选择素水平存在显著差异。在不同类别之间进行比较时，rs6136和rs6127存在显著差异。此外，与对照组相比，具有单倍型AAA、AGA和AGG的患者的sP-选择素水平显著更高。在非常高风险和高风险类别中，sP-选择素水平存在显著差异。在不同类别之间进行比较时，AGA和AGG单倍型存在显著差异。所研究的SELP基因多态性与T2DM患者的sP-选择素水平以及血管风险显著相关。
