sFlt-1基因rs4769613位点多态性与云南地区不同海拔子痫前期的相关性研究

Association of sFlt-1 gene rs4769613 loci polymorphism with pre-eclampsia at different altitudes in Yunnan Province

摘要:

目的： 探讨可溶性Fms样酪氨酸激酶1（soluble Fms-like tyrosine kinase 1，sFlt-1）基因rs4769613位点多态性与云南地区不同海拔子痫前期（preeclampsia，PE）的相关性。方法： 选取2018年1月至2019年12月在云南省第一人民医院产科分娩的124例汉族孕妇（低海拔组），其中PE孕妇61例，正常足月孕妇63例，同期在迪庆藏族自治州人民医院产科分娩的122例汉族孕妇（高海拔组），其中PE孕妇61例，正常足月孕妇61例，提取外周血DNA，采用TaqMan探针实时荧光PCR技术检测sFlt-1基因的rs4769613位点基因型分布和等位基因频率。结果： ①长期生活及居住在云南高原环境低海拔地区和高海拔地区的孕妇存在sFlt-1基因rs4769613位点多态性。②高海拔地区PE组TT、CC、TC基因型分别占18.03%（11/61）、29.51%（18/61）、52.46%（32/61）；高海拔地区对照组TT、CC、TC基因型分别占34.43%（21/61）、21.31%（13/61）、44.26%（27/61）；低海拔地区PE组TT、CC、TC基因型分别占13.11%（8/61）、27.87%（17/61）、59.02%（36/61）；低海拔地区对照组TT、CC、TC基因型分别占30.16%（19/63）、25.40%（16/63）、44.44%（28/63）。③高海拔地区，PE组TT基因型分布明显低于对照组（18.03% vs.34.43%，P=0.039，OR=0.419，95%CI=0.181~0.970）；但高海拔地区PE组CC、CT基因型相较于对照组无明显差异。在低海拔地区，PE组TT基因型分布明显低于对照组（13.11% vs.30.16%，P=0.021，OR=0.349，95%CI=0.139~0.875），但低海拔地区PE组CC、CT基因型相较于对照组无明显差异。高海拔地区PE组与低海拔地区PE组之间、高海拔地区对照组与低海拔地区对照组之间，TT、TC、CC基因型表达无明显差异。结论： sFlt-1基因SNP rs4769613 C>T可能与云南高原地区孕妇PE发病有关；sFlt-1基因中TT基因型可能是云南高原地区孕妇PE的保护因素；同样处于云南高原低氧环境下，不同海拔地区的PE孕妇之间及正常孕妇之间sFlt-1基因的rs4769613位点基因型分布无统计学差异。

Abstract:

Objective: To explore if any difference exists in genotypic distribution and allele frequency of sFlt-1 gene rs4769613 loci polymorphism in patients with preeclampsia (PE) at relatively low and high altitudes in Yunnan Province. Methods: A total of 124 pregnant women of Han nationality who gave birth in the obstetrics department of Yunnan First People's Hospital from January 2018 to December 2019 were selected as the low altitude group, including 61 PE pregnant women and 63 normal full-term pregnant women, and 122 pregnant women of Han nationality who gave birth in the obstetrics department of Diqing Tibetan Autonomous Prefectural People's Hospital during the same period, including 61 PE pregnant women and 61 normal full-term pregnant women were selected into the high altitude group. We investigated the genotypic distribution and allele frequency of sFlt-1 gene at rs4769613 locus by performing TaqMan probe real-time fluorescence PCR on them. Results: Firstly, we did find rs4769613 loci polymorphism of sFlt-1 gene in PE and control groups for both low and high altitude of Yunnan. Secondly, TT, CC and TC genotype in PE group at high altitude accounted for 18.03% (11/61), 29.51% (18/61) and 52.46% (32/61) respectively. Compared to control group at high altitude, TT, CC and TC genotype frequency accounted for 34.43% (21/61), 21.31% (13/61) and 44.26% (27/61). In the PE group at low altitude, TT, CC and TC genotype accounted for 13.11% (8/61), 27.87% (17/61) and 59.02% (36/61) respectively, and in the control group at low altitude, TT, CC and TC genotype accounted for 30.16% (19/63), 25.40% (16/63) and 44.44% (28/63). Thirdly, TT genotype distribution in the PE group were significantly lower than that in the control group (18.03% vs.34.43%, P=0.039, OR=0.419, 95%CI=0.181-0.970), but there were no significant differences in CC and CT genotype between the PE group and the control group at high altitude area. The TT genotype distribution in the low altitude PE group were significantly lower than that in the control group (13.11% vs.30.16%, P=0.021, OR=0.349, 95%CI=0.139-0.875), but there was no significant difference in CC and CT genotype between the low altitude PE group and the low altitude control group. There were no significant differences in the expression of TT, TC and CC genotype between PE group at high altitude and control group at low altitude. Conclusion: The SNP rs4769613 C>T of sFlt-1 gene may be related to the pathogenesis of PE in pregnant women, and the TT genotype of sFlt-1 gene may have protective effect on PE in pregnant women at Yunnan Plateau. There was no significant difference in the genotype distribution and allele frequency of The SNP rs4769613 of sFlt-1 gene between pregnant women with PE nor normal pregnant women in Yunnan Plateau.