dc.description.abstract | High plasma level of Lp(a) (>25~30 mg/dl)
is one of the major risk factors for coronart
atherosclerosis and its major complication,
but is different from LDL by the large
glycoprotein named apolipoprotein(a)
(apo(a)). The kringle IV domain of apo(a) is
variously repeated form about 15 to 40 times
in individual, resulting in a large number of
molecular weight isoforms of the protein.
The significance of Lp(a) on coronary heart
disease (CHD) and the genetic bases for the
variation in plasma Lp(a) concentration for
population in Taiwan are, however, not
understood. In a prospective Chin-Shan
Community Cardiovascular (CCC) study,
the Lp(a) plasma level showed a skew
distribution (mean 14.3 mg/dl, medium 9.0
mg/dl, n=3453). A hospital-based study in
National Taiwan University Hospital
(NTUH) disclosed higher Lp(a) levels in
patients with than those without significant
coronary lesions (33.0 ± 21.9 versus 23.6 ±
17.6 mg/dl, n = 381, P<0.0001). Sixteen
isoforms of apo(a) have been identified
based on electromobility, including 5 F-forms,
1 B-form, 9 S-forms and a null form.
Seventy four percent of the subjects have
two bands, 23.1 % have single band and 2.6
% are null type, and six cases of them
contain both S-and F-forms. Subjects
containing F- or null form have high Lp(a)
level than subjects containing S-form (45.6
± 19.5 versus 21.5 ± 13.1 mg/dl, p<0.0001).
Subjects containing larger apo(a) isoforms
(S5-S9) have lower risk of CAD than those
having smaller isoforms (S1-S4) (0.51, n =
164 versus 0.68, n = 93; p<0.01). For
subjects (n = 47) with plasma Lp(a) level
disproportion to its apo(a) size, the TTTTA-repeats
in the 5'-control region of the apo(a)
gene was analyzed by polymerase chain
reaction and nucleotide sequencing. The
majority have 7 (8.5%), 8 (42.5%), or 9
(42.5%) repeats. Only 1 case (2.1%) for 4, 5,
and 6 repeats, individually. There is no
significant correlation between the number
of TTTTA repeats and plasma Lp(a)
concentration. We conclude that the apo(a)
size polymorphism, but not TTTTA repeats
in the 5’ control region, significantly
correlated with the plasma Lp(a) level,
which in turn correlated with the prevalence
of CAD in our study group. These results
would be helpful in the prevention and
treatment of CAD in Taiwan. | en |