Association of Complement Factor D and H Polymorphisms with Recurrent Pregnancy Loss.

Hee Young Cho,Eun Hee Ahn,Eun Ju Ko,Chang Soo Ryu,Nam Keun Kim,Han Sung Park,Woo Sik Lee,Jung Oh Kim,Young Ran Kim

doi:10.3390/ijms21010017

Abstract

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation, and the incidence of RPL is estimated at 1% of all pregnancies. While the etiologies of RPL are diverse, immune function is considered to be an important cause of RPL. In particular, the complement system is essential for stable development of the placenta and fetus. Moreover, complement factor D (CFD) and complement factor H (CFH) are important regulators of the complement system and are associated with diseases, such as age-related macular degeneration. Therefore, we investigated whether polymorphisms of CFD and CFH are associated with RPL in 412 women with RPL and 384 control women. Genotyping of three polymorphisms (CFD rs2230216, CFH rs1065489, and CFH rs1061170) was performed by TaqMan probe real-time PCR and PCR-restriction fragment length polymorphism. Association of three polymorphisms with RPL was evaluated by statistical analysis. The GT/TC genotype combination of CFH rs1065489 G>T/CFH rs1061170 T>C was associated with a decreased risk of RPL occurrence compared with reference genotypes (adjusted odds ratio [AOR] = 0.439; 95% confidence interval [CI] = 0.238–0.810; p = 0.008), and this association remained significant after adjustment for multiple comparisons using false discovery rate (FDR) correction (p = 0.040). In addition, the CFH rs1065489G>T polymorphism is associated with homocysteine and prolactin level and CFH rs1061170 TC genotype is related to uric acid and triglycerides level in RPL patients. Therefore, those factors could be possible clinical risk factors in RPL patients.

Highlights

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation [1,2]
We evaluated the relationship between complement factor H (CFH) and complement factor D (CFD) polymorphisms and susceptibility to RPL
Analysis of the genotype frequencies of CFD and CFH in RPL patients and controls (Table 2) revealed that the CFH rs1061170 T>C polymorphism was significantly associated with RPL risk, this association did not remain significant after adjustment using the false discovery rate [FDR] correction (p = 0.116)

Summary

Introduction

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation [1,2]. In cases with identifiable causes, genetic disorders, such as fetal chromosomal abnormalities; maternal factors, including anatomical deformities, placental anomalies, thrombophilia, endocrine disorders, immune dysfunction, infection, smoking, psychological trauma, and stress; and environmental factors have been implicated in RPL [6,7] Among these factors, immune function is considered an important cause of RPL, as pregnancy induces a complex immune response at the implantation site to facilitate and protect the pregnancy and prevent response to the “foreign” fetus [8]. C3 is essential for the activation of the classical and alternative pathways of the complement system This factor plays an important role in early placental development, and several C3 gene variants have been found in association with idiopathic RPL [14,15,16]. We evaluated the relationship between CFH and CFD polymorphisms and susceptibility to RPL

Results

Subjects

Genotyping

Assessment of Clinical Risk Factors

Data Analysis