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P07 Phenotype expression in Italian families with familial combined hyperlipidemia (FCHL): The familial combined hyperlipidemia genetic study
S13
PO5
PO7
NITRITE, ENDGTHBLIN AND E-SELECTIN PLASMA LEVELS AFTER ARGININB INFUSION IN NORMAL AND VASCIJLOPATHIC SUBJECTS Fe&o S., G&i M. Chair of Semeiologyand Medical Methodology,Garibaldi Hospital, Universityof Catania
Phenotype expression in Italian families with Familial Combined Hyperlipidemia (FCHL): The Familial Combined Hyperlipidemia Genetic Study. Arca M.. Mont& A.. *Gaddi A, *Cialletti C , *Sanglorgi % (‘ampagna F., Flora L.. Porcu L., Cantini R., RICCI G lstltuto di Terapia Medica Sistemattca, Universiti di Roma “La Sapien&, *lXpartimento di Medicina Clinica e Biotecnologica I!nwersita di Bologna My
The authorscarried out a study on the simultaneousmcdifications of nitrite, end&&m and E-s&ctin plasma levels a& infusion of arginine (a precursorof nitric oxide endethehalsynthesis)in normal and vasculopathic subjects. The series consisted of 24 female subjects(meanage 5827) of which: 12 normalcontrols; 12 suffering from chronic cerebralvascular diseaseand coronaryheart diseases. Eachsubject,after a venousblood withdrawal, receivedarginine(20 g over 2 hours); the withdrawal was repeatedat first and second hour. On each plasma sample were determinedthe levels of total nitrites (NOT‘, eeiorimetric method), endothehn (ET-l, ELISA method)and E-selectin(B-s, ELISA method).The levels of NO,, specificend-productsof nitric oxide, did not showsignificantchanges after arginineinfusionin the vasculopathicsubjects(groupB); in the normalsubjects(group A) a significant reductionwas recorded.The ET-l levels a&r a&tine did not show significant differences betweenthe two group. ‘Ihe values of E-s presentedno significant variations after arginine in the two groups. The basal values of nitrites, endothelin and E-se&tin resulted significantly (P
FCHL is characterised by the elevation of VLDL, LDL or both in plasma and by the expressloo of multiple-type hyperlipidemia in the relatws of the proband. Although several genes have been proposed as candidate genes. the genetic defects responsible for FCHL remain unknown. Within the framework of an ongoing study aimed at identifying the susceptibility loci for this lipid disorder (FCHI.-Tclcthon Stody), we identified 20 large Italian families wth FCHL (302 subjects). The phenotypic characteristics of these families are described in order to examine the role of different diagnostic criteria for FCHL and evaluate some factors that affect expression of lipid phenotype The inclusion criteria for probaods were: 1) total cholesterol (TC) and/or triglycerides (TG) and/or apoltpoprotem B (alnB) ?age-sex specific 901h percentde: 2) at least one first degree relative with a different hyperlipemic phenotype: 3) absence of tendon xantbomas; 4) no sqs of diabetes. At present data on lipid and anthropametric measurements are available for 168 subjects. Eighty-seven (51 3%) showed normal lipid profile and 81 (48.7%) were defined as affected. Probands were 9 (45% ) type IIB, 9 (45%) type IV and 2 (10%) Isolated hyperap& ‘The overall phenotype distribution among affected mdwlduals was I4 type IIA (17.3%), I4 type IIB (17.3%), 35 type IV (43.2%) and I8 isolated hyperapoB (22.2%). Plasma lipid levels II) the different phenotypes are reported helow
PO6 COMPLEMENT SYSTEM, IMMUNE COMPLEXES AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH AND WITH HY PERCHOLESTEROLEMIA ATHEROSCLEROSIS. Pasqui A.L., Bova G., Bruni F., Pompella G., Cercignani M. e Auteri A. Dpt of Internal Medecine and Immunology. University of Siena. Italy. Atherosclerosis lesions share the characteristics of a chronic inflammatory reaction and of lipid accumulation. The aim of this study is to assessthe relations between lipid and inflammatory factors in a group of hypercholesterolemic subjects and in a group of normolipemic patients with clinical atherosclerosis compared with matched normal subjects. In particular we evaluated the complement system and the circulating immune complexes containing cholesterol (chol-CIC) and related them with the serum levels of cholesterol and HDL-chol. In addition we evaluated the levels of the adhesion molecule ICAM- as a sign of endothelial dysfunction. We found a significant increase of chol-CIC and of complement terminal complex C5b-9 in hypercholesterolemic subjects compared with patients with atherosclerosis and with control group. Also patients with atherosclerosis presented an increase of these parameters, significant as regards CSb-9. In hyper- cholesterolemic patients the most elevated values were found in patients who had lower values of HDL-chol. Both groups of patients with dyslipidemia and with atherosclerosis showed a significant increaseof ICAM1. Several components may be involved in thesephenomena; the complement activation may be induced by the increasedimmune complexes, but may be also induced by the decrease of complement regulatory proteins vehiculated by the HDL. In addition the complement changesmay be related to the variations of other humoral and cell systems (endothelium, coagulativelfibrinolytic system) whose involvement is suggested in our study by the changesof ICAM- 1.
Lipids -mq!dl TC HDL-C TG LDL-C apo B
Normnl~
Type IIA
189.0 + 34.6 299.4 A 36.7 539: I2 I 55.5 f 17.9 102.2 i 4-1.8 160 4 + 46 3 113 7i298 211.8i 32.0 YJOi21 I 1622,436
Type IIB 306.7 + 23.8 42.8 z 13.6 296.3 2 37 8 207.1 228.0 171.3?271
Type IV---228.0 41.3; 339.2 124.5 139.5
+ 33 9 12.6 : 126.7 + 33.3 + -32 9
Isolated byper apoB 237.0 + 23 9 51.7: 13.7 156.0 f 46.2 154.0 k 22 9 155.4 + I4 5
In thzse familtes type IV and isolated hyperapoB appear to be Ihe most common llpid phcnotypcs among FCHL rclatwes. Severe-to-moderate elevation of apoB win the hpld abnomrahi) almost conamtly observed m FClIl mdwduals
PO8 Regional Screening for FB Pakrmo-2 Mutation: Identification Cluster in Sicily
of a
Cefaii A.B., Emmanoele G., Maria0 G., De AngeRs L, Caldarella R., Amore M.G., !3esti E., Barbagrllo CM., Bertolini S., Notarbartolo A., Averna M., Travali S. University of Palermo; University Genor, Italy.
of Catania and University
of
FH Palerme- mutation is a LDL receptor gene mutatigl first described in a hyperchokerolemic Sicilian path. It is a missense mutation of the axon 8, producing a ‘DC tmnsversien(Cys243Arg). Ihe mutation intmduceaa PstI restriction site, which &wed us to design a PCRdigestien based labmatory sbategy for mutaticn rapid ScreeniJlg. We used the fdhnving primers: S’
PO5
PO7
NITRITE, ENDGTHBLIN AND E-SELECTIN PLASMA LEVELS AFTER ARGININB INFUSION IN NORMAL AND VASCIJLOPATHIC SUBJECTS Fe&o S., G&i M. Chair of Semeiologyand Medical Methodology,Garibaldi Hospital, Universityof Catania
Phenotype expression in Italian families with Familial Combined Hyperlipidemia (FCHL): The Familial Combined Hyperlipidemia Genetic Study. Arca M.. Mont& A.. *Gaddi A, *Cialletti C , *Sanglorgi % (‘ampagna F., Flora L.. Porcu L., Cantini R., RICCI G lstltuto di Terapia Medica Sistemattca, Universiti di Roma “La Sapien&, *lXpartimento di Medicina Clinica e Biotecnologica I!nwersita di Bologna My
The authorscarried out a study on the simultaneousmcdifications of nitrite, end&&m and E-s&ctin plasma levels a& infusion of arginine (a precursorof nitric oxide endethehalsynthesis)in normal and vasculopathic subjects. The series consisted of 24 female subjects(meanage 5827) of which: 12 normalcontrols; 12 suffering from chronic cerebralvascular diseaseand coronaryheart diseases. Eachsubject,after a venousblood withdrawal, receivedarginine(20 g over 2 hours); the withdrawal was repeatedat first and second hour. On each plasma sample were determinedthe levels of total nitrites (NOT‘, eeiorimetric method), endothehn (ET-l, ELISA method)and E-selectin(B-s, ELISA method).The levels of NO,, specificend-productsof nitric oxide, did not showsignificantchanges after arginineinfusionin the vasculopathicsubjects(groupB); in the normalsubjects(group A) a significant reductionwas recorded.The ET-l levels a&r a&tine did not show significant differences betweenthe two group. ‘Ihe values of E-s presentedno significant variations after arginine in the two groups. The basal values of nitrites, endothelin and E-se&tin resulted significantly (P
FCHL is characterised by the elevation of VLDL, LDL or both in plasma and by the expressloo of multiple-type hyperlipidemia in the relatws of the proband. Although several genes have been proposed as candidate genes. the genetic defects responsible for FCHL remain unknown. Within the framework of an ongoing study aimed at identifying the susceptibility loci for this lipid disorder (FCHI.-Tclcthon Stody), we identified 20 large Italian families wth FCHL (302 subjects). The phenotypic characteristics of these families are described in order to examine the role of different diagnostic criteria for FCHL and evaluate some factors that affect expression of lipid phenotype The inclusion criteria for probaods were: 1) total cholesterol (TC) and/or triglycerides (TG) and/or apoltpoprotem B (alnB) ?age-sex specific 901h percentde: 2) at least one first degree relative with a different hyperlipemic phenotype: 3) absence of tendon xantbomas; 4) no sqs of diabetes. At present data on lipid and anthropametric measurements are available for 168 subjects. Eighty-seven (51 3%) showed normal lipid profile and 81 (48.7%) were defined as affected. Probands were 9 (45% ) type IIB, 9 (45%) type IV and 2 (10%) Isolated hyperap& ‘The overall phenotype distribution among affected mdwlduals was I4 type IIA (17.3%), I4 type IIB (17.3%), 35 type IV (43.2%) and I8 isolated hyperapoB (22.2%). Plasma lipid levels II) the different phenotypes are reported helow
PO6 COMPLEMENT SYSTEM, IMMUNE COMPLEXES AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH AND WITH HY PERCHOLESTEROLEMIA ATHEROSCLEROSIS. Pasqui A.L., Bova G., Bruni F., Pompella G., Cercignani M. e Auteri A. Dpt of Internal Medecine and Immunology. University of Siena. Italy. Atherosclerosis lesions share the characteristics of a chronic inflammatory reaction and of lipid accumulation. The aim of this study is to assessthe relations between lipid and inflammatory factors in a group of hypercholesterolemic subjects and in a group of normolipemic patients with clinical atherosclerosis compared with matched normal subjects. In particular we evaluated the complement system and the circulating immune complexes containing cholesterol (chol-CIC) and related them with the serum levels of cholesterol and HDL-chol. In addition we evaluated the levels of the adhesion molecule ICAM- as a sign of endothelial dysfunction. We found a significant increase of chol-CIC and of complement terminal complex C5b-9 in hypercholesterolemic subjects compared with patients with atherosclerosis and with control group. Also patients with atherosclerosis presented an increase of these parameters, significant as regards CSb-9. In hyper- cholesterolemic patients the most elevated values were found in patients who had lower values of HDL-chol. Both groups of patients with dyslipidemia and with atherosclerosis showed a significant increaseof ICAM1. Several components may be involved in thesephenomena; the complement activation may be induced by the increasedimmune complexes, but may be also induced by the decrease of complement regulatory proteins vehiculated by the HDL. In addition the complement changesmay be related to the variations of other humoral and cell systems (endothelium, coagulativelfibrinolytic system) whose involvement is suggested in our study by the changesof ICAM- 1.
Lipids -mq!dl TC HDL-C TG LDL-C apo B
Normnl~
Type IIA
189.0 + 34.6 299.4 A 36.7 539: I2 I 55.5 f 17.9 102.2 i 4-1.8 160 4 + 46 3 113 7i298 211.8i 32.0 YJOi21 I 1622,436
Type IIB 306.7 + 23.8 42.8 z 13.6 296.3 2 37 8 207.1 228.0 171.3?271
Type IV---228.0 41.3; 339.2 124.5 139.5
+ 33 9 12.6 : 126.7 + 33.3 + -32 9
Isolated byper apoB 237.0 + 23 9 51.7: 13.7 156.0 f 46.2 154.0 k 22 9 155.4 + I4 5
In thzse familtes type IV and isolated hyperapoB appear to be Ihe most common llpid phcnotypcs among FCHL rclatwes. Severe-to-moderate elevation of apoB win the hpld abnomrahi) almost conamtly observed m FClIl mdwduals
PO8 Regional Screening for FB Pakrmo-2 Mutation: Identification Cluster in Sicily
of a
Cefaii A.B., Emmanoele G., Maria0 G., De AngeRs L, Caldarella R., Amore M.G., !3esti E., Barbagrllo CM., Bertolini S., Notarbartolo A., Averna M., Travali S. University of Palermo; University Genor, Italy.
of Catania and University
of
FH Palerme- mutation is a LDL receptor gene mutatigl first described in a hyperchokerolemic Sicilian path. It is a missense mutation of the axon 8, producing a ‘DC tmnsversien(Cys243Arg). Ihe mutation intmduceaa PstI restriction site, which &wed us to design a PCRdigestien based labmatory sbategy for mutaticn rapid ScreeniJlg. We used the fdhnving primers: S’