Association of kinase insert domain-containing receptor (KDR) gene polymorphism/haplotypes with recurrent spontaneous abortion and genetic structure

<bold>Background: </bold> Recurrent spontaneous abortion is one of the diseases that can lead to physical, psychological, and, economical problems for both individuals and society. Recently a few numbers of genetic polymorphisms in kinase insert domain-containing receptor (KDR) gene are examined that can endanger the life of the fetus in pregnant women. <bold> </bold>Objective:<bold> </bold> The risk of KDR gene polymorphisms was investigated in Iranian women with idiopathic recurrent spontaneous abortion (RSA). <bold> </bold>Materials and Methods:<bold> </bold> A case controlled study was performed. One hundred idiopathic recurrent spontaneous abortion patients with at least two consecutive pregnancy losses before 20 weeks of gestational age with normal karyotypes were included in the study. Also, 100 healthy women with at least one natural pregnancy were studied as control group. Two functional SNPs located in KDR gene; rs1870377 (Q472H), and rs2305948 (V297I) as well as one tag SNP in the intron region (rs6838752) were genotyped by using PCR based restriction fragment length polymorphism (PCR-RFLP) technique. Haplotype frequency was determined for these three SNPs' genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to study genetic variation. <bold> </bold>Results:<bold> </bold> Functional SNP (rs1870377) was highly linked to tag SNP (rs6838752) (D value=0. 214; chi(2) = 16.44, p<0. 001). K means clustering showed that k = 8 as the best fit for the optimal number of genetic subgroups in our studied materials. This result was in agreement with Neighbor Joining cluster analysis. <bold> </bold>Conclusion:<bold> </bold> In our study, the allele and genotype frequencies were not associated with RSA between patient and control individuals. Inconsistent results in different populations with different allele frequencies among RSA patients and controls may be due to ethnic variation and used sample size.