Abstract
Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integrin B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for ITGB8 gene were tested for associations with ICH risk, lobar ICH risk and non-lobar ICH after adjustment for age, gender, history of hypertension and country of origin. Linear regression models were used to test the effect of tag SNPs on the ICH age of onset. Correction for multiple comparisons was carried out. The rs7565633 tag SNP of the ITGAV gene was independently associated with the risk of lobar ICH in the codominant model of inheritance [odds ratio (95 % confidence interval (CI)) 0.56 (0.36–0.86), p = 0.0013]. Furthermore, heterozygous individuals of the rs10251386 and the rs10239099 of the ITGB8 gene had significantly lower age of ICH onset compared to the wild-type genotypes [regression coefficient (b) −3.884 (95 % CI −6.519, −1.249), p = 0.0039 and b = −4.502 (95 % CI −7.159, −1.845), p = 0.0009, respectively]. The present study provides preliminary indication for an influence of ITGAV gene tag SNP in the development of lobar ICH and of ITGB8 gene variants in the age of ICH onset.
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The study was supported in part by a research grant of the Research Committee of the University of Thessaly, Greece (Code: 2845).
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Efthimios Dardiotis and Vasileios Siokas authors have equally contributed to this study.
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Supplementary figure 1
Tag-SNPs of ITGAV gene (chr2: positions 187,163,045 to 187,253,872) retrieved from the International HapMap Project for CEU population (http://hapmap.ncbi.nlm.nih.gov, Release 27, Phase II + III, Feb09, on NCBI B36 assembly, dbSNP b126) (PDF 3246 kb)
Supplementary figure 2
Tag-SNPs of ITGB8 gene (chr7: positions 20,337,250 to 20,421,903) retrieved from the International HapMap Project for CEU population (http://hapmap.ncbi.nlm.nih.gov, Release 27, Phase II + III, Feb09, on NCBI B36 assembly, dbSNP b126)(PDF 4876 kb)
Supplementary figure 3
Pairwise LD between the studied ITGAV tag SNPs (rs3911239, rs3911238, rs7596996, rs7585471, rs4667108, rs9333290, rs7589470, rs7565633, rs2595389, rs12620821, rs11902171) and LD blocks (from left to right D’, r2, GOLD heatmap) (PDF 8523 kb)
Supplementary figure 4
Pairwise LD between the studied ITGB8 tag SNPs (rs206198, rs7456987, rs3757725, rs10251386, rs3807941, rs10239099, rs3757727, rs2107129, rs717861, rs752474, rs739752) and LD blocks (from left to right D’, r2, GOLD heatmap) (PDF 7688 kb)
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Dardiotis, E., Siokas, V., Zafeiridis, T. et al. Integrins AV and B8 Gene Polymorphisms and Risk for Intracerebral Hemorrhage in Greek and Polish Populations. Neuromol Med 19, 69–80 (2017). https://doi.org/10.1007/s12017-016-8429-3
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DOI: https://doi.org/10.1007/s12017-016-8429-3