1st Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary.
BMC Med Genet. 2010 Feb 11;11:25. doi: 10.1186/1471-2350-11-25.
Several studies have shown overexpression of leptin in microarray experiments in pre-eclampsia (PE) and in hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We decided to study four leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients by using quantitative real-time PCR and melting curve analysis.
DNA was isolated from blood samples from 83 normotensive pregnant women and 75 HELLP syndrome patients. Four SNPs, LEPR c.326A>G (K109), LEPR c.668A>G (Q223R), LEPR c.1968G>C (K656N) and LEPR c.3024A>G (S1008) were determined by quantitative real-time PCR and melting curve analysis. Investigators were blinded to clinical outcomes.
LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C and LEPR c.3024A>G allele, genotype and haplotype polymorphisms were not different in HELLP syndrome patients and normotensive healthy pregnants. There were strong linkage disequilibrium (LD) between loci c.326A>G and c.6687A>G (D' = 0.974), and c.668A>G and c.1968G>C (D' = 0.934), and c.326A>G and c.1968G>C (D' = 0.885), and c.1968G>C and c.3024A>G (D' = 1.0). However, linkages of c.3024A>G with c.668A>G (D' = 0.111) and c.326A>G (D' = 0.398) were weak. The Hardy-Weinberg equilibrium was observed for all polymorphisms. However the LEPR c.326A>G AG genotype was twice more frequent and the (AG AG GG AG) haplotype was three times more frequent in HELLP syndrome patients. The introduced quantitative real-time PCR combined with melting curve analysis is a fast and reliable method for the determination of LEPR SNPs.
Although certain LEPR haplotypes are more frequent in HELLP syndrome, we conclude that there is no compelling evidence that the four studied LEPR SNP polymorphisms associated with the development of HELLP syndrome.
多项研究表明，在子痫前期（PE）和溶血、肝酶升高、血小板减少（HELLP）综合征的微阵列实验中，瘦素表达过度。我们决定通过定量实时 PCR 和熔解曲线分析来研究 HELLP 综合征患者的四种瘦素受体（LEPR）SNP 多态性。
从 83 名血压正常的孕妇和 75 名 HELLP 综合征患者的血液样本中分离出 DNA。通过定量实时 PCR 和熔解曲线分析确定四种 SNP，即 LEPR c.326A>G（K109）、LEPR c.668A>G（Q223R）、LEPR c.1968G>C（K656N）和 LEPR c.3024A>G（S1008）。研究人员对临床结果进行了盲法评估。
LEPR c.326A>G、LEPR c.668A>G、LEPR c.1968G>C 和 LEPR c.3024A>G 等位基因、基因型和单倍型多态性在 HELLP 综合征患者和血压正常的健康孕妇中无差异。在 c.326A>G 和 c.6687A>G（D'=0.974）、c.668A>G 和 c.1968G>C（D'=0.934）、c.326A>G 和 c.1968G>C（D'=0.885）以及 c.1968G>C 和 c.3024A>G（D'=1.0）之间存在强烈的连锁不平衡（LD），但 c.3024A>G 与 c.668A>G（D'=0.111）和 c.326A>G（D'=0.398）之间的连锁较弱。所有多态性均符合哈迪-温伯格平衡。然而，在 HELLP 综合征患者中，LEPR c.326A>G AG 基因型更为常见，（AG AG GG AG）单倍型更为常见三倍。所引入的定量实时 PCR 结合熔解曲线分析是一种快速可靠的 LEPR SNP 检测方法。
尽管某些 LEPR 单倍型在 HELLP 综合征中更为常见，但我们认为没有令人信服的证据表明这四种研究的 LEPR SNP 多态性与 HELLP 综合征的发展有关。
