HLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This study aimed to analyze whether HLA-G polymorphic variations (G*0103, G*0104, and G0105N) are related to the risk of RPL in women from Kashmir, North India.

A total of 200 women who suffered ≥2 RPLs and 240 healthy controls were recruited from the same geographical region. Additionally, 100 spouses of RPL affected women and 60 products of conception were evaluated. HLA-G genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.

The variant genotype 0103:0103 in exon 2 of HLA-G was not detected. The genotype 0104/0105 was detected in 100% of RPL patients, spouses, and controls. Exon 2 and variant genotypes G*0103 in exon 2 and G*0105 in exon 3 of HLA-G were absent in our population and thus did not contribute to the etiopathogenesis of RPL. In contrast, the exon 3 HLA-G variant G*0104N was significantly more frequent in RPL patients and their spouses compared to the control group (p<0.05). The presence of the HLA-G variant genotype G*0104N (exon 3) was detected in 13% of RPL patients and 7% of their male partners, indicating a significantly higher frequency than in controls and suggesting a substantial risk for RPL (p<0.05).

This study revealed that the higher frequency of the HLA-G*0104 allele in both partners strongly predicted a substantial risk for RPL in our population.