Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family

Abstract

Objective The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) in protein C (PROC) and protein S (PROS1) genes with deep venous thrombosis (DVT) in a thrombophilia family. Methods DNA were extracted from blood of participants. Five PROC SNPs and 11 PROS1 SNPs were selected from the Hapmap and 1000 Genomes databases. The minor allele frequencies (MAFs) of SNPs in the thrombophilia family (Group I) and healthy controls (Group II) were detected. SNPs were analysed by Chi‐square, logistic regression and linkage disequilibrium patterns. Results MAFs for all 16 SNPs were greater than 0.05. Chi‐square analysis showed significant differences between Group I and Group II in the frequency of mutant alleles of rs1799808, rs5936, rs6123, rs12634349, rs6441600 and rs13062355 SNPs (P < .05). Logistic regression analysis found that mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT in this family (OR > 1, L95 > 1). Linkage disequilibrium was found among 15 of the PROC and PROS SNPs. Conclusions Single nucleotide polymorphisms (SNPs) of PROC and PROS1 may be closely associated with DVT in this thrombophilia family. Mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT, whereas mutant alleles of rs1799810, rs6123 and rs12634349 may protect individuals from DVT. With the exception of rs9681204, there was linkage disequilibrium between PROC and PROS1 SNPs. We found that 12 haplotypes were in linkage disequilibrium, but linkage disequilibrium was strong in only eight of these (frequency >5%).

Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels

“…[1][2][3][4] Genetic variants in the protein-coding genes for antithrombin, PC, and PS (SERPINC1, PROC, and PROS1, respectively) [5][6][7] have been studied for decades, and rare mutations have been associated both with low protein levels and with risk of VTE. 5,[8][9][10][11] There have been at least 6 agnostic genome-wide association studies (GWAS) for antithrombin, PC, and PS, with sample sizes ranging from 351 (antithrombin) to 13 968 (PC). For antithrombin, no additional genome-wide significant loci beyond SERPINC1 were identified.…”

Antithrombin, protein C and protein S: Genome and transcriptome wide association studies identify 7 novel loci regulating plasma levels

“…Antithrombin, protein C (PC), and protein S (PS) are circulating anticoagulant proteins, and low levels or low activity of these proteins are associated with the risk of venous thromboembolism (VTE) [1][2][3][4][5] . Variation in the protein-coding genes for antithrombin, PC, and PS (SERPINC1, PROC, and PROS1, respectively) [6][7][8] has been studied for decades, and rare mutations have been associated both with low protein levels and with risk of VTE 6,[9][10][11][12] . There have been at least 6 agnostic genome-wide association studies (GWAS) for antithrombin, PC, and PS, with sample sizes ranging from 351 (GAIT, antithrombin) to 13,968 (ARIC, PC).…”

Genetic factors that may affect the risk of developing thrombosis in patients with myeloproliferative disorders

“…Moreover, mutations and polymorphisms in the PROC and PROS1 genes are associated with thrombotic disease [16][17][18][19][20].…”