Objective: Leptin signaling plays an important role in regulating metabolism and reproduction. In the present study, we investigated the relationship between polymorphisms of leptin receptor (LEPR) gene A223G and A668G and preeclampsia (PE) and evaluated influences of genotypes on clinical, metabolic, and oxidative stress indices in Chinese women.
Methods: This is a case-control study including 322 patients with PE and 1295 healthy pregnant women. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragments length polymorphism method. Clinical and biochemical parameters were analyzed.
Results: The frequencies of the AA + AG genotypes (28.6% vs. 36.1%) and A allele (14.9% vs. 19.8%) of LEPR A223G polymorphism, and those of the AA + AG genotypes (17.7% vs. 24.6%) and A allele (9.0% vs. 12.9%) of LEPR A668G polymorphism were significantly lower in the PE group than those in the control group. The 223A and 668A alleles were protective factors against PE in the regression model, which included age and delivery body mass index as covariates (OR = 0.684, 95% CI: 0.506-0.926, p = .014; OR = 0.650, 95% CI: 0.456-0.927, p = .017, respectively). When the 668GG/223GG combined genotype served as the reference category, the 668A/223A combined allele had further enhanced the protective effect on PE (OR = 0.558, 95% CI: 0.374-0.833, p = .004). Patients possessing the LEPR 223A allele had higher total antioxidant capacity and lower oxidative stress index (p < .05), while those with the LEPR 668A allele had higher high-density lipoprotein cholesterol levels (p = .045) compared with those carrying the corresponding GG genotype.
Conclusions: The 223A and 668A alleles of LEPR polymorphisms are genetic protective factors for PE in Chinese women. The two alleles may exert a beneficial effect on oxidative stress and lipid metabolism in patients.
Keywords: Preeclampsia; genetic polymorphism; leptin receptor; lipid metabolism; oxidative stress.