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. 2014 Mar 12;1(4):239–250. doi: 10.1002/acn3.48

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© 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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SRP9 expression and sequencing in patients with mTLE and/or FS. (A) SRP9 mRNA levels (normalized qPCR data: Rn) in hippocampal homogenates of autopsy controls (Control; n = 15; Rn = 112.3 ± 12.3) and mTLE patients without (non-HS; n = 19; Rn = 100.0 ± 8.2) and with hippocampal sclerosis (HS; n = 21; Rn = 209.0 ± 24.4). (F_2,52 = 12.023, P = 0.0001; non-HS vs. HS: P = 0.008; Control vs. HS: P = 0.001; Control vs. non-HS: P = 1.000). SRP68 mRNA levels did not differ between groups (Control Rn = 107.8 ± 17.6; non-HS Rn = 100.0 ± 8.1; HS Rn = 115.1 ± 19.3; F_2,36 = 0.203, P = 0.817. (B) SRP9 protein (insert shows Western blot with loading control β-actin) in hippocampal homogenates of Controls (n = 6; 53.9 ± 12.2), non-HS (n = 12; Rn = 100.0 ± 11.6), and HS (n = 11; Rn = 223.2 ± 47.6) patients. (F_2,26 = 6.685, P = 0.005; non-HS vs. HS: P = 0.023; Controls vs. HS: P = 0.009; Controls vs. non-HS: P = 1.000). Error bar indicates SEM. *Significantly different after multiple testing correction P < 0.01. (C) Sequencing of SRP9 exons, intron/exon boundaries and promoter region (5 kb) in healthy controls (n = 169), mTLE patients (n = 368) and mTLE patients with FS (n = 91) revealed a significant (P < 0.01 bold) difference in allele frequencies of one common promoter SNP (rs12403575 G/A) in mTLE patients. P-value corrected for multiple SNP testing P < 0.01. All SNPs in the sequenced region with an allele frequency >0.05 were selected for the assocation study. In the HS group 46% had antecedent FS, in the non-HS group only 6%. (D) Further single SNP analysis using a larger control cohort (n = 730) identified a significant association between rs12403575 and mTLE (n = 368, P = 0.01, odds ratio (OR) = 1.238). This association was replicated in patients with FS without mTLE (n = 236, P = 0.038, OR = 1.212). (E) Patients with AA genotype had a significantly (F_2,33 = 4.142, P = 0.023) higher hippocampal SRP9 expression (Rn = 169.7 ± 22.9) than patients with AG genotype (Rn = 105.9 ± 13.1, P = 0.044), and GG genotype (Rn = 103.1 ± 19.6, P = 0.058). Data are expressed as means ± SEM. *Significantly different P < 0.05.