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3.2 Regulation of Autonomic Activity and Blood Pressure
by CHGA Promoter SNPs
A UCSD study used the HAP algorithm to ascertain physiological significance of
promoter SNPs in five tightly linked common promoter variants (at positions
C-1014T, G-988T, C-415T, and A-89C), which inferred three most common haplo-
types: haplotype A (TTGTC, 56.9%), haplotype B (CGATA, 23%), and haplotype
C (TTGCC, 16.5%). Of these haplotypes, haplotype B was found to blunt the blood
pressure (BP) response to cold stress, which included immersion of the left hand in
ice water for 60 s after a 10 min rest upon arrival and continuous recording of BP
and heart rate with a calibrated radial artery applanation device. Interestingly, the
Fig. 3 Functional variation in the CHGA promoter and validation by changes in nucleotide in
the haplotype. (a) Circle represents promoter haplotypes, and the circle area represents overall
frequency. The proportion of the individual haplotype frequency in each of the four populations
(indicated by different colors) is shown by the subdivision within the circle. Dashed lines indi-
cate alternative topologies of equal length. Lines connecting haplotypes indicate nucleotide sub-
stitution. (b) Association of CHGA promoter SNP (GG, TG, and TT) with plasma CgA peptides.
(c) Haplotype (haplotype 1–8)-specific CHGA promoter activity as evaluated by luciferase
reporter activity with transfected promoter/reporter plasmids in PC12 cells. (d) Role of nucleo-
tide substitution in haplotype 1 (T-1014C, T-988G, and G-462A) or haplotype 6 (C-1014T,
G-988T, and A-462G) in CHGA promoter activity as evaluated by luciferase reporter activity
with transfected promoter/reporter plasmids in PC12 cells (Reprinted with permission from
ELSEVIER Publishing Company)
Chromogranin A SNPs and Disease Association