Department of Biochemistry and Molecular Biology, Faculty of Medicine, Al-Neelain University, PO BOX 12702, Khartoum, Sudan.
Department of Obstetrics and Gynecology, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia.
BMC Med Genet. 2020 Aug 17;21(1):162. doi: 10.1186/s12881-020-01104-z.
Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia.
A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted.
Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98-10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15-10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77-113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09-0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16-11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D' = 1, r = 0.012).
Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.
瘦素受体基因（LEPR）变体可能影响瘦素水平，并作为子痫前期的风险因素。在苏丹的子痫前期妇女中研究了 LEPR 基因两个错义变体 rs1137101（c.668A>G）和 rs1805094（c.1968G>C）。
2018 年 5 月至 12 月在苏丹喀土穆的 Saad Abualila 妇产医院进行了匹配的病例对照研究（每组 122 名妇女）。病例为子痫前期妇女，对照组为健康孕妇。使用聚合酶链反应-限制性片段长度多态性对 LEPR 基因变体 c.668A>G 和 c.1968G>C 进行基因分型。使用 logistic 回归模型（调整年龄、产次、体重指数和血红蛋白水平）进行分析。
在对照组中，LEPR 基因变体 c.668A>G 和 c.1968G>C 的基因型频率符合 Hardy-Weinberg 平衡（P>0.05）。与对照组相比，LEPRc.668A>G 变体中的等位基因 G 在病例中更为常见[43.4% vs. 10.2%；OR=6.44；95%CI（3.98-10.40）；P<0.001]。在 LEPRc.668A>G 变体中，AG 基因型是病例中比对照组更常见的基因型，与子痫前期风险显著相关[37.7% vs. 15.5%；AOR=3.48；95%CI（1.15-10.54）；P=0.027]。同样，与对照组相比，GG 基因型是病例中第二常见的基因型，与子痫前期风险相关[24.6% vs. 2.5%；AOR=14.19；95%CI（1.77-113.76）；P=0.012]。LEPRc.1968G>C 变体的任何基因型均与子痫前期无关。病例和对照组均未检测到 CC 基因型。该人群中 70.1%的常见单倍型为 A-G，它显著降低子痫前期的风险[OR=0.14；95%CI（0.09-0.23）；P<0.001]。然而，26.8%的 G-G 单倍型与子痫前期风险显著相关[OR=6.70；95%CI（4.16-11.05）；P<0.001]。c.668A>G 和 c.1968G>C 两个变体均处于强连锁不平衡状态（D'=1，r=0.012）。
我们的数据表明，rs1137101（c.668A>G）变体和 G-G 单倍型可能独立与子痫前期的发生相关。
