A Field Synopsis and Meta-Analysis of Genetic Association Studies in Peripheral Arterial Disease: The CUMAGAS-PAD Database

Abstract

In an electronic search of the literature, the authors systematically retrieved all published studies that investigated genetic susceptibility to peripheral arterial disease (PAD). They created a comprehensive database of all eligible studies, collecting detailed genetic and bioinformatics data on each polymorphism. Data from eligible studies were synthesized using meta-analysis techniques. Gene variants were classified into distinct pathophysiologic pathways, and their potential involvement in PAD pathogenesis was determined. Forty-one publications that examined 44 gene polymorphisms were included. For 37 polymorphisms, the variant form had a functional effect. Twenty-three polymorphisms in 22 potential PAD candidate genes (F2, FGB, MTHFR, ITGB3, ACE, AGT, IL6, CCL2, ICAM1, SELE, MMP9, PPARG, MMP1, ADD1, P2RY12, LIPC, PLA2G7, SCARB1, MMP3, MTTP, LPA, CHRNA3) showed a significant association in individual studies. Eighty-eight percent of the studies had statistical power of less than 50%, and in 15 studies the genotype distribution in the control group did not conform to Hardy-Weinberg equilibrium. Data on 12 polymorphisms (F5 1691 G/A, MTHFR 677C/T, F2 20210 G/A, ITGB3 1565 T/C, ACE I/D, AGT 704C/T, AGT -6G/A, AGT 733C/T, IL6 -174 G/C, MMP9 -1562C/T, ICAM1 1462A/G, CHRNA3 831C/T) were synthesized, and a positive association was found for 3 (IL6 -174 G/C, ICAM1 1462A/G, CHRNA3 831C/T).