Familial Defective Apolipoprotein B100, assessed by PCR techniques in French patients with isolated hypercholesterolemia

J Mel

Cell

Cardiol

118 kmitiat in

23

(Supplement

thfecth

French

LOUX N., BOILEAU C. U73 INSERM, Lapeyronie, 34059

patients

IV)

(1991)

A-With

isolated

8100, assesscd by hypercholesterolemia.

C., BENLIAN P., CAMBOU J.P.1, DENAT M.1, MONNlER Chateau de Longchamp, 75016 PARIS. 1, CHU Purpan, MONTPELLIER

FCR

L.*,PERCHERONC.*, 31939 TOULOUSE.

techniques

3,

JUNlEN HopM

are now identified at the molecular Two genetic disorders causing type Ila hypercholesterolemia, level. Besides LDL receptor defects, are defects of its natural ligand, Apolipoprotein BIOO. The latter corresponds to a unique point mutation at residue 3500 of the mature protein. To evaluate the showing familial type Ila prevalence of this disorder in a population of French subjects hypercholesterolemia, PCR amplification was performed on the ApoB gene sequence surrounding residue 3500. A number of 101 subjects had plasma LDL-cholesterol levels above 5 mmol/l, and normal triglycerides and RDL cholesterol. Their genomic DNA was amplkled and a screening test, using the AS0 technique was then performed. Only one subject was heteroxygous for the mutation. We further : ApaLI, Hincll, Pvull, Xbal, Mspl. EcoRI, and 3’ PCR analyzed the 7 following polymorphic markers HVR. Until1 now, the genotype observed In this subject Is compatible with the previously described haplotype. A complete haplotype characterization will be presented and will indicate if this mutation shares a common origin with the previously described. These results indicate that a second genetic defect in cholesterol homeostasls is implicated at a frequency of approximately I%, in French familial type Ila hypercholesterolemic subjects.

119 PREFERENTIAL OCCUPANCYOF HIGH AFFINITY CARDIAC Na,K-ATPase, ISOENZYMES (I or 43) BY LND 7% DURING POSITIVE INOTROPY IN THE DOG. J.M. Maixent, R.iv?. Kawamoto,J.R. Skoster,B.M. HalprynandS.Fenard.Laboratoire Nativelle,Longjumeau, France,andNorwichEatonPharmaceuticals Inc., Norwich,N.Y. USA Ventricular cardiomocytesfrom variousspecies (dog,ferret andrat) containat leasttwo isoformsor Na,K-ATPase.In rat, the inotropicandtoxic arrhythmoeniceffects are seenonly after an isoformwith a low affinity receptorhasbeenoccupiedb digitalis. In contrastit hasnot beenclear1 determinedwhetheroccupancyof the secondtype of isoformb low concentrations or*dtgoxin,of ouabain,leadsto positiveinotropyin dog. To avoidiii neticproblemsparticularto the do8’ caused~~~~;p$?o~ -g!;!tgw rate of onsetof actionwith suchdrugsandto etermine with a highaffinity receptorcouldbeinhibitedduringinotro y, wemeasured in vivo the bloodlevelsof LND 796,a semisynthetic cardiacglycosidetlf at hasa rapid onsetof activity. Circulatingbloodlevelsof LND 796weredeterminedat characteristictimesof than e of inotropyin the dogby an e atic assaythat measures the inhibitionof Na,9 -ATPaseactivity. The sameassay T asbeenusedto correlatethe bloodlevelsof LND 796with inhibitionof specificisoformsin sarcolemma preparations.

120

SIGNIFICANCE OF RESIDUAL STRESS ISCHENIA ASSESSED BY THALLIUN 201 TONOSCINTIGRAPHY WITH REST REINJECTION IN WST PTCA PATIENTS. Gilles Karcher, Yves Juilliere, Alain Bertrand, Pierre Y. Marie.Nicolas Danchin, Francois Cherrier. Department of Cardiology, CHU Nancy-Brabois, 54500, France. The aim of the study was to determine the significance of residual stress ischemia evidenced using Tl 201 tomoscintigraphy with rest reinjection in pts with (SI) previous PTCA. Quantitative coronary angiography was performed to determine the minimal lumen diameter at the stenosis site (MLD) and the presence of restenosis > SO%, using the CAAS system on end-diastolic still-frames of 77 dilated segments in 68 consecutive pts who underwent 6-mth post-PTCA coronary angiography preceded by Ex-SPECT with rest reinjection. The scintigraphic data were scored by 2 blinded observers ; SI was defined as the presence of a stress defect, reversible after rest reinjection, in the territory of the dilated artery. Results : Pts with SI (n=27) have a lower MLD than those without SI (n=50) (1.0+0.6 vs 1.7f0.6, pcn.oool\. In addition, even in pts without restenosis (n=54), the presence of SI corresp3ndea to a iower MLD than thal 05 pts witnour S1 <1.5?0.3 vs l.iliG .?, (n=q), p 50% restenosis ; in the remaining l/3, the presence of a low MLD might explain the persistence of stress ischemia. 5.40