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

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.

Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

“…An association with miscarriage was suggested but not significant, and needs to be evaluated in larger cohorts, similar to studies that identified complement variants important in atypical hemolytic uremic syndrome. A different study found that a polymorphism in Factor H was associated with a decrease in risk of recurrent pregnancy loss ( 68 ). Factor H in part controls complement activation on cells by binding to sialic acid.…”

Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors—A Preliminary Study

“…It is estimated that RPL affects over 1% of the general population and only half of the cases can be explained after a medical investigation. Each miscarriage increases the risk of another miscarriage to 15% [ 2 , 3 ]. Recurrent pregnancy loss [ 2 ] was defined according to the WHO definition as three or more consecutive spontaneous miscarriages before the 20th week of gestation [ 4 , 5 ].…”

“…Each miscarriage increases the risk of another miscarriage to 15% [ 2 , 3 ]. Recurrent pregnancy loss [ 2 ] was defined according to the WHO definition as three or more consecutive spontaneous miscarriages before the 20th week of gestation [ 4 , 5 ]. ESHRE guidelines indicated immunological diagnostics in case of two idiopathic pregnancy losses [ 1 ].…”

Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

“…Several gene polymorphisms affect the risk of RPL, such as matrix metalloproteinase genes [36], the methylenetetrahydrofolate reductase (MTHFR) gene [37], complement factors D and H [38], and genome wide methylation analysis [39], reflecting the complicated mechanisms that underlie the development of RPL. Previous studies have investigated the association of high levels of homocysteine and low levels of folate with the risk of RPL [40,41].…”