Table 4.
Effect of the ECE-1c repeat polymorphisms on the promoter activity in neuronal cells
| Diagnosis | RLA [−1; −586]/RLA[−1; −512] mean | RLA [−1; −586]/RLA [−1; −512] SD | Matrix (CA[bp]-CpG[bp]-CA[bp]) of the transfected plasmid |
|---|---|---|---|
| Valsartan study | 1.12 | 0.11 | 6-0-34 |
| Control | 0.95 | 0.38 | 6-14-36 |
| Valsartan study | 1.36 | 0.72 | 6-14-40 |
| AD | 1.13 | 0.18 | 6-16-30 |
| Control | 0.89 | 0.23 | 6-16-32 |
| AD | 1.34 | 0.17 | 6-16-32 |
| Control | 1.48 | 0.20 | 6 bp(CA)-16 bp(CpG)-[14 bp(CA)-2 bp(CG)-18 bp(CA)] |
| AD | 1.00 | 0.02 | 6-16-38 |
| Control | 1.51 | 0.16 | 6-18-32 |
| Control | 1.36 | 0.52 | 6-18-32 |
| AD | 1.04 | 0.30 | 6-18-32 |
| Valsartan study | 1.09 | 0.30 | 6-18-34 |
| Valsartan study | 1.23 | 0.04 | 6-18-34 |
| AD | 1.05 | 0.07 | 6-18-34 |
| Valsartan study | 1.25 | 0.18 | 6-18-36 |
| Control | 1.08 | 0.36 | 6-18-36 |
| Valsartan study | 1.26 | 0.03 | 6-18-38 |
| Control | 1.68 | 0.76 | 6-18-38 |
| AD | 1.41 | 1.25 | 6-18-38 |
| Control | 1.13 | 0.15 | 6-18-38 |
| Control | 0.90 | 0.24 | 10-18-42 |
| Valsartan study | 1.39 | 0.19 | 6-20-32 |
| Control | 0.95 | 0.22 | 6-20-40 |
| Control | 1.44 | 0.31 | 6-20-42 |
| Valsartan study | 2.73 | 1.19 | 6-22-26 |
| AD | 6.60 | 1.35 | 6-22-38 |
| Valsartan study | 0.84 | 0.15 | 6-22-42 |
| AD | 1.13 | 0.06 | 6-22-44 |
| Valsartan study | 1.66 | 0.91 | 6-22-50 |
| Control | 3.08 | 0.54 | 6-24-40 |
| Control | 0.05 | 0.04 | 6 bp(CA)-[8 bp(CG)-2 bp(CA)-2 bp(CG)]-32 bp(CA) |
| AD | 1.08 | 0.19 | 8-16-34 |
Two serial deletion mutants ([−1; −512] without the repeat and [−1; −586] comprising the repeat (compare Fig. 7) of multiple human haplotypes of the ECE-1c promoter were transiently transfected into KELLY cells (2–5 independent transfections, each n = 4). RLAs are defined as the renilla-standardized and pGL3-basic-normalised firefly luciferase promoter activities, e.g., RLA [−1; −586] = ([−1; −586]-pGL3-basic(firefly)/phRL-null(renilla))/(insertless pGL3-basic(firefly)/phRL-null(renilla)). The ratio RLA [−1; −586] construct/RLA [−1; −512] construct indicates the contribution of the microsatellite to the total promoter activity. “Control” refers to the German Dementia Competence Network study. “Matrix” denotes the individual haplotype (CA repeat [length in bp]-CpG repeat [length in bp]-CA repeat [length in bp]) of the transfected plasmid preparation. Please note that different individuals can share an identical matrix. Bold characters represent unusual repeat compositions or extreme RLA ratios, respectively. The identity of the region [−1; −512] in both constructs ([−1; −512]/pGL3-basic and [−1; −586]/ pGL3-basic) was confirmed by sequencing to exclude effects of SNPs located downstream of the microsatellite.