HSPA1L rs1061581 polymorphism is associated with the risk of preeclampsia in Han Chinese women.

Jinbao Zong,Qingwu Tian,Shengjun Li,Guirong Sun,Kaiqiu Chu,Shiguo Liu,Yan Lin,Xin Zhao,Bing Jiang

doi:10.1042/bsr20194307

Abstract

Preeclampsia (PE) is an excessive systemic inflammation response with dysfunction of endothelial. As a stress protein, heat shock protein 70 (HSP70) plays a pivotal role in protecting cells against apoptosis, oxidative damage and genetic damage. In humans, three genes encode members of the HSP70 class: HSPA1A, HSPA1B and HSPA1L. Our study was to investigate the association between genetic variations of HSPA1L and the susceptibility for PE in Chinese Han population. The polymorphisms of rs2227956, rs1043618 and rs1061581 in HSPA1L were genotyped by TaqMan allelic discrimination real time polymerase chain reaction (PCR) in 929 PE patients and 1024 healthy pregnant women. Statistic difference of the genotypic and allelic frequencies were found in HSPA1L rs1061581 between PE patients and controls (χ2 = 29.863, P < 0.001 by genotype; χ2 = 27.298, P < 0.001, OR = 1.874, 95%CI 1.476–2.379 by allele) and HSPA1L rs1061581 A alleles occurred more frequently in PE patients compared with healthy controls (PE vs. controls 10.28% vs. 5.76%). Furthermore, we divided the PE cases into early-onset/late-onset PE and mild/severe PE subgroups and found statistical differences in genotypic and allelic frequencies of the HSPA1L rs1061581 between early-onset PE, late-onset PE, mild PE, severe PE and controls, respectively. Moreover, HSPA1L rs1061581 A alleles were more frequent in early-onset PE, late-onset PE, mild PE and severe PE than controls respectively. Therefore, we concluded that HSPA1L rs1061581 polymorphism is associated with the risk of PE in Han Chinese women and A alleles may play a role in the susceptibility for PE.

Highlights

Pre-eclampsia (PE) is a pregnancy-specific syndrome characterized by de novo hypertension and/or proteinuria (>300 mg/24 h) that occurs after 20 weeks of gestation in pregnancies, and is always accompanied with multiorgan disorders, which affects the maternal and fetal mortality and morbidity severely [1,2,3]
For the PE patients and healthy pregnant women, we found a significant difference in genotypic and allelic frequencies of HSPA1L rs1061581 polymorphism (χ2 = 29.863, P < 0.001 by genotype; χ2 = 27.298, P < 0.001, odds ratios (ORs) = 1.874, 95%confidence intervals (CIs) 1.476–2.379 by allele), and HSPA1L rs1061581 A alleles occurred more frequently in PE patients compared with healthy controls (PE vs. controls 10.28% vs. 5.76%)
It is becoming increasingly accepted that oxidative stress, and maternal systemic inflammatory response have a key role in the pathogenesis of PE [8,15,16], which may induce the expression of heat shock protein 70 (HSP70) [18]

Summary

Introduction

Pre-eclampsia (PE) is a pregnancy-specific syndrome characterized by de novo hypertension (systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg) and/or proteinuria (>300 mg/24 h) that occurs after 20 weeks of gestation in pregnancies, and is always accompanied with multiorgan disorders, which affects the maternal and fetal mortality and morbidity severely [1,2,3]. As a multifactorial disorder affecting about 5–7% of all women during pregnancy, to date, a number of studies have been carried out to explore the mechanisms of PE, including hereditary variants, inflammation, immunological imbalance and oxidative stress and so on, the specific pathogenesis has not yet been fully explained [4,5,6]. Some inflammatory cytokines, such as IL-1β, IL-2, IL-6 and IFN-γ, were higher in the serum of PE patients than that of normotensive pregnancies [10,11,12], suggesting that inflammation may be involved in the pathogenesis of PE strongly. Oxidative stress and maternal systemic inflammatory response, which play important roles in the pathogenesis of PE, have been shown to induce the expression of HSP70 [18]. We designed this study to examine whether polymorphisms of three tag SNPs (rs2227956, rs1043618 and rs1061581) in HSPA1L, which is one of the three genes encoding HSP70 proteins [22], were associated with the risk of PE or not

Materials and methods

Result

Findings

Discussion