Chromogranins from Cell Biology to Physiology and Biomedicine

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718 female) subjects drawn from 53,078 individuals (27,475 women, 25,538 men)
recruited from a large primary care (Kaiser Permanente) population in San Diego.
Of note, Gly364Ser variant was associated with lower BP in the San Diego popula-
tion (Rao et al. 2007 ) (Fig. 6a) Seventeen Gly364Ser heterozygote (as cases) and
48 Gly364/Gly364 homozygote (as controls) individuals underwent cold pressor
test, 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. Although resting BP and HR did not differ signifi-
cantly between the groups, Gly364Ser heterozygotes displayed decreased BP rise
after cold pressor test (by ~16/~8 mm Hg) (Rao et al. 2007 ). Gly364Ser heterozy-
gotes differed significantly with the controls in the time domain of autonomic
monitoring: increased baroreceptor slope during upward deflections (by ~47%)
and downward deflections (by ~44%), increased parasympathetic index by

0

4 10^4

3 10^4

2 10^4

1 10^4

NE EPI

p=0.047

p=0.003

Gly/Gly (n=236)

Stimulus: nicotine (60mm)

Human catestatin (mm)

Net

3 H-norepinephrine release

(% of control)

Wild-type human catestatin: (hCHGA352-372: IC 50 ~0.77 μM)

Gly364Ser human catestatin: (IC 50 ~3.59 μM)

Pro370Leu human catestatin: (IC 50 ~0.33 μM)

0.01

0

20

40

60

80

100

120

0.11 10

Gly364Ser

Pro370Leu Wt

Gly/Ser (n=13)

ac

b

Renal catecholamine

Excretion (ng/gm creatinine)

Fig. 5 (a) Sequence alignment showing sequence conservation across several species at Gly364Ser
and Pro370Leu regions. (b) Potencies of CST variants (WT-CST, Gly364Ser-CST, and Pro370Leu-
CST) on nicotine-evoked catecholamine secretion from PC12 cells (Reprinted with permission
from ELSEVIER Publishing Company). (c) Effects of Gly364Ser variants on catecholamine
secretion

Chromogranin A SNPs and Disease Association