Assessment of Kir Genes in the Venezuelan Ad-Mixed Population with Either Idiopathic Recurrent Pregnancy Loss or Unexplained Infertility

Killer-cell immunoglobulin-like receptors (KIRs) play a crucial role in the cytotoxic activity of natural killer (NK) cells, encompassing both inhibitory and activating types. A higher ratio of cytotoxic to inhibitory receptors may harm successful pregnancies by disrupting the uterine environment. Ongoing debates surround the impact of KIR gene variations on recurrent pregnancy loss (RPL) and infertility across populations. This study aimed to explore KIR gene polymorphisms in RPL and infertility among the Venezuelan admixed population. The Venezuelan population exhibits a genetic mix of Caucasian, African, and local Amerindian ancestry, distinguishing it from other Latin American admixed populations. This study included 100 controls and 86 patients: 73 women with idiopathic RPL (53 primary and 20 secondary) and 13 infertile patients (4 primary and 9 secondary). The frequency of activating receptors KIR2DS2 and KIR2DS3 was significantly lower (p < 0.05) in the whole patient group compared to controls. However, when analyzing the haplotypes and genotypes, the significance between patients and controls was lost. When comparing RPL and infertile patients, KIR2DS2, KIR2DL3, 2DL5, and 3DL1 were significantly less frequent in infertile women. In infertile women, KIR2DS3 frequency was increased compared to controls and RPL. The results suggest that the frequency of inhibitory receptors may differentiate patients with RPL and infertility. Further studies should ascertain the expression and function of KIRs in uterine NK cells in patients with RPL and infertility.