C-reactive protein gene variants associated with recurrent pregnancy loss independent of CRP serum levels: A case-control study

• Serum CRP levels are elevated in pregnancy and higher in adverse pregnancy outcomes.
• Mean serum CRP levels were higher in women with recurrent pregnancy loss.
• Carriage of CRP rs2794520 was associated with significant increases in CRP levels.
• Both RPL-susceptible and RPL-protective CRP genotypes were identified.

The aim of this study is to investigate the association of recurrent pregnancy loss (RPL) with altered C-reactive protein (CRP) serum levels, and genetic variation in CRP gene. This was a retrospective case–control study, involving 275 women with three or more consecutive pregnancy losses, and 290 age-matched control women, who were recruited from outpatient obstetrics/gynecology clinics. CRP serum levels (hs-CRP) were determined by latex-enhanced nephelometry, and CRP genotyping was done by allelic discrimination. Mean serum CRP levels were higher in RPL cases than in control women, and carriage of the (minor) T allele of rs2794520 was associated with significant increase in CRP levels (P = 0.017). Minor allele frequency (MAF) of rs7553007 was significantly different between RPL cases and control women, and was associated with reduced risk of RPL after adjusting for BMI and menarche. There was a significant enrichment of minor allele-carrying genotypes of rs1130864 and rs1417938 SNPs, and reduced frequency of minor allele-carrying genotypes of rs876537, rs2794520, and rs7553007 in RPL cases, thus assigning RPL-susceptible and -protective nature to these genotypes, respectively. Carriage of (minor) T allele of only rs2794520 was associated with significant increase in CRP levels. CRP variants that influenced circulating CRP levels in chronic inflammatory conditions are also associated with RPL, pointing to CRP as RPL candidate gene.