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Grossly elevated serum lipoprotein(a) levels in young women with endometriosis
Poster session abstracts/Atherosclerosis 115 (SuppL ) (1995) $45-S129 P l l Lipoprotein (a)
$89
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THE INCIDENCE OF DOUBLE-BANDED APO(A) PHENOTYPES IN A HEALTHY NORMOLIPIDEMIC DUTCH POPULATION OF CAUCASI AN DESCENT P.F.C.C.M. Duif F.R. Leus, H . A Kleinveld. H.J.M. van Rijn Department of Clinical Chemistry, University Hospital Utrecht, The Nether lands
DIFFERENCES IN SERUM CONCENTRATION AND PHENOTYPE DISTRIBUTION OF LP(al BETWEEN BLACK AND WHITE POPULA TIONS W Riesen ~, H. Engler ~, P Bovel 3, R. Darioli 3, M. Abel 3 qnst f Clio Chem & Hematol, State Hospilal. St. Gallen, Switzerland: 21nst de Med Soc ct Prev~ Universit6 de Lausanne, Switzerland: 3Unity of Prey & Contr ot Vase Dis, Ministry of Health. Seychelles
Lp(a) is a genetic variant of LDL containing an extra subunit called apolipoprotein(a), (apo(a)). The concentration of Lp(a) is mainly genetically determined with an apparent inverse correlation between the apo(a) size and the Lp(a) concentration in plasma. Lp(a) plasma concentrations above 300 mg/L are considered to infer a 2- to 5-fold increase in the incidence of atherosclerosis. Apo(a) shows great homology with plasminogen and consists mainly of kringle 4, kringle 5 and an inactive protease domain. The apo(a) size and pbenotype is determined by the number of multiple copies kringle 42. In this report we describe the incidence of the apo(a) phenotype The geometrical overall mean Lp(a) concentration in the studied population of healthy normolipidemic volunteers of Caucasian descent (n= 185) was 79 mg/L with a range of 14 mg/L up to 993 mg/L without a significant difference between women (n=93) and men (n=92). Of the subjects 20% (n=37) had a Lp(a) concentration above 300 mg/L. Using the SDS/agarose electrophoretic technique followed by semi d D, immunobJoning and the numerical system as described by Kamboh et a! with number I for the largest apo{a) phenotype and number 24 for the smallest apo(a) phenotype none of the subjects was characterized as having an apo(a) phenotype above number 21. The 11% (n=21) characterized as a not-detected apo(a) pheno type had in all cases a Lp(a) concentration below the detection limit of the IRMA assay (14 mg/L). In this study we characterized 25% (n=46) of the subjects as double-banded phenotypes, a remarkable low percentage. Despite the fact that two apo(a) alleles are present in every subject we conclude, based on the present results and those of others, that in the majority of healthy Caucasians only a single apo(a) phenotype in plasma is detectably expressed.
It is known that Black populations display an almost normal distribution of Lp~a) serum values and higher mean concentrations than Whites, who show a very skewed distribution. Whether both populations share differences in concemranon within a given phenotype of Lpta) is not known so far. We have determined the serum concentralion ol Lp(a) by means of a IWO site inmrunoradiometrlc procedure using two monoclonal antibodies against apo~al IPharmacia) and the 6 major isoforms by means of SDS-PAGE in 306 Black Seychellois and in 406 Swiss (MONICAI. Statistical analyses were pcrlorrned by two-way ANOVA. Black Seychellois showed a significantl3 higher mean concenlranon of Lp(a) (p < 0.001) The isoform $4 ',x~a~ Ihc most frequent phenotype in both populations. However there were sllghl dillcrences 112 inlgration belween the Sa isotorms of the two groups. Tire median of Lpla) within the $4 isoform was higher in the Seychellois than the Swiss /171 vs 65rag/I). The heterozygous phenotype $3S4 was the second most frequent phenotype observed in Seychellois (14 %). In the Swiss population dais phenotype was only seen in 6.9 % {sixth most trequent/ Similarl}, to $4 the Seychellois had a higher concentration in $3S4 than the Swiss {312 vs 120 rag/l). The $3 phenotype was in both populations on the third place (Seychellois 8 %, Swiss 12,6 %, median Seychellois 265 vs l lgmg,I in Swiss) The phenotype $2 was never observed in the Se,,chellois gruup, in Swiss in 7 , 1 % {fifth place). The data indicate that Blacks do not only show a different phenotype distribution than Whites, but that ther~ also exhibit a higher LpIa) concentration within a given phenotype.
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A P O L I P O P R O T E I N ( A ) Kpnl G E N O T Y P E D I S T R I B U T I O N IN W E S T G R E E N L A N D ESKIMOS DIFFERS F R O M C A U C A S I A N DANES L. Lemming, I.C. Klausen, H.S. Pedersen, A. Hvnlby, S. Moiler, U. Gerdes. G Mulvad, P.S. Hansen, P Bjerregaard, O. Faergeman Department of Internal Medicine and Cardiology A, Aarhus University Hospital, 8000 Aarhus C
G R O S S L Y E L E V A T E D S E R U M LIPOPROTEIN(a) L E V E L S IN YOUNG WOMEN WITH ENDOMETRIOSIS D. Crook, M. Sidhu, R. Howell, D.K. Edmonds, J.C. Stevenson W y n n Department of Metabolic Medicine, National Heart and Lung Institute, London
W e have compared apo(a/ Kpol genotype distributions and Lp(a) concentrations in 96 West Greenland Eskimos from Uummannaq with those in 455 Danish reference men. Apo(a) Kpnl genotypes were determined by pulsed-field gel electrophoresis followed by hybridisation with a kringle-4 specific probe. Lp(a) concentrations were measured with a two-site immunoradiometric assay. The distribution of apo(a) Kpnl alleles were significantly different in West Greenland Eskimos and Caucasian Danes ( P < 0 . 0 0 0 0 l ) ; the genotypes, comprising any a l l e l e < n u m b e r 13, which correspond to protein phenotypes F, B. S I and $2, were less frequent among Eskimos. whereas genotypes, comprising any a l l e l e > n u m b e r 13 were more frequent. The median Lp(a) concentration in Eskimos (11.5 mg/dl) was significantly higher than in Caucasian Danes (6,33 mg/dl). W e conclude that other factors than apo(a) Kpni genntype determine Lp(a) concentrations in West Greenland Eskimos.
Serum lipoprotein(a) [Lp(a)] has been implicated in atherogenesis. Although case-control studies show higher Lp(a) levels in subjects with C H D , not all epidemiological studies support a causal rote in the disease. This conflict would be explained if Lp(a) is an acutephase protein, a role supported by the demonstration of functional interleukin-6 regulatory elements in the apo(a) gene promoter. High levels of activated macrophage products are found in the peritoneal fluid of women with endometriosis, a common disorder in which endometrial tissue is found outside of the lining of the uterine cavity. We studied 39 women with endometriosis and 39 healthy matched controls. Serum levels of lipid, lipoproteins and apolipoproteins were similar in the two groups, except for five-fold higher Lp(a) levels in w o m e n with endometriosis (median 15.0 mg/dl [range 0.05-87.3 mg/dl] vs. 3.0 mg/dl [0.05-29.0 mg/dl] in controls; P < 0 . O 0 1 ) . This loo difference remained highly significant after adjustment for differences in age, height, adiposity and Lp(a) 60[smoking. This study provides further evidence that Lp(a) is an (mg/dl) 40 -acute phase reactant and challenges the view that serum L p ( a ) l e v e l s 20 ~ will provide useful information _t 0 Cases Controls about a healthy individual's C H D (n=39) (n=39) risk.
Serum80I
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$89
331
333
THE INCIDENCE OF DOUBLE-BANDED APO(A) PHENOTYPES IN A HEALTHY NORMOLIPIDEMIC DUTCH POPULATION OF CAUCASI AN DESCENT P.F.C.C.M. Duif F.R. Leus, H . A Kleinveld. H.J.M. van Rijn Department of Clinical Chemistry, University Hospital Utrecht, The Nether lands
DIFFERENCES IN SERUM CONCENTRATION AND PHENOTYPE DISTRIBUTION OF LP(al BETWEEN BLACK AND WHITE POPULA TIONS W Riesen ~, H. Engler ~, P Bovel 3, R. Darioli 3, M. Abel 3 qnst f Clio Chem & Hematol, State Hospilal. St. Gallen, Switzerland: 21nst de Med Soc ct Prev~ Universit6 de Lausanne, Switzerland: 3Unity of Prey & Contr ot Vase Dis, Ministry of Health. Seychelles
Lp(a) is a genetic variant of LDL containing an extra subunit called apolipoprotein(a), (apo(a)). The concentration of Lp(a) is mainly genetically determined with an apparent inverse correlation between the apo(a) size and the Lp(a) concentration in plasma. Lp(a) plasma concentrations above 300 mg/L are considered to infer a 2- to 5-fold increase in the incidence of atherosclerosis. Apo(a) shows great homology with plasminogen and consists mainly of kringle 4, kringle 5 and an inactive protease domain. The apo(a) size and pbenotype is determined by the number of multiple copies kringle 42. In this report we describe the incidence of the apo(a) phenotype The geometrical overall mean Lp(a) concentration in the studied population of healthy normolipidemic volunteers of Caucasian descent (n= 185) was 79 mg/L with a range of 14 mg/L up to 993 mg/L without a significant difference between women (n=93) and men (n=92). Of the subjects 20% (n=37) had a Lp(a) concentration above 300 mg/L. Using the SDS/agarose electrophoretic technique followed by semi d D, immunobJoning and the numerical system as described by Kamboh et a! with number I for the largest apo{a) phenotype and number 24 for the smallest apo(a) phenotype none of the subjects was characterized as having an apo(a) phenotype above number 21. The 11% (n=21) characterized as a not-detected apo(a) pheno type had in all cases a Lp(a) concentration below the detection limit of the IRMA assay (14 mg/L). In this study we characterized 25% (n=46) of the subjects as double-banded phenotypes, a remarkable low percentage. Despite the fact that two apo(a) alleles are present in every subject we conclude, based on the present results and those of others, that in the majority of healthy Caucasians only a single apo(a) phenotype in plasma is detectably expressed.
It is known that Black populations display an almost normal distribution of Lp~a) serum values and higher mean concentrations than Whites, who show a very skewed distribution. Whether both populations share differences in concemranon within a given phenotype of Lpta) is not known so far. We have determined the serum concentralion ol Lp(a) by means of a IWO site inmrunoradiometrlc procedure using two monoclonal antibodies against apo~al IPharmacia) and the 6 major isoforms by means of SDS-PAGE in 306 Black Seychellois and in 406 Swiss (MONICAI. Statistical analyses were pcrlorrned by two-way ANOVA. Black Seychellois showed a significantl3 higher mean concenlranon of Lp(a) (p < 0.001) The isoform $4 ',x~a~ Ihc most frequent phenotype in both populations. However there were sllghl dillcrences 112 inlgration belween the Sa isotorms of the two groups. Tire median of Lpla) within the $4 isoform was higher in the Seychellois than the Swiss /171 vs 65rag/I). The heterozygous phenotype $3S4 was the second most frequent phenotype observed in Seychellois (14 %). In the Swiss population dais phenotype was only seen in 6.9 % {sixth most trequent/ Similarl}, to $4 the Seychellois had a higher concentration in $3S4 than the Swiss {312 vs 120 rag/l). The $3 phenotype was in both populations on the third place (Seychellois 8 %, Swiss 12,6 %, median Seychellois 265 vs l lgmg,I in Swiss) The phenotype $2 was never observed in the Se,,chellois gruup, in Swiss in 7 , 1 % {fifth place). The data indicate that Blacks do not only show a different phenotype distribution than Whites, but that ther~ also exhibit a higher LpIa) concentration within a given phenotype.
332
334
A P O L I P O P R O T E I N ( A ) Kpnl G E N O T Y P E D I S T R I B U T I O N IN W E S T G R E E N L A N D ESKIMOS DIFFERS F R O M C A U C A S I A N DANES L. Lemming, I.C. Klausen, H.S. Pedersen, A. Hvnlby, S. Moiler, U. Gerdes. G Mulvad, P.S. Hansen, P Bjerregaard, O. Faergeman Department of Internal Medicine and Cardiology A, Aarhus University Hospital, 8000 Aarhus C
G R O S S L Y E L E V A T E D S E R U M LIPOPROTEIN(a) L E V E L S IN YOUNG WOMEN WITH ENDOMETRIOSIS D. Crook, M. Sidhu, R. Howell, D.K. Edmonds, J.C. Stevenson W y n n Department of Metabolic Medicine, National Heart and Lung Institute, London
W e have compared apo(a/ Kpol genotype distributions and Lp(a) concentrations in 96 West Greenland Eskimos from Uummannaq with those in 455 Danish reference men. Apo(a) Kpnl genotypes were determined by pulsed-field gel electrophoresis followed by hybridisation with a kringle-4 specific probe. Lp(a) concentrations were measured with a two-site immunoradiometric assay. The distribution of apo(a) Kpnl alleles were significantly different in West Greenland Eskimos and Caucasian Danes ( P < 0 . 0 0 0 0 l ) ; the genotypes, comprising any a l l e l e < n u m b e r 13, which correspond to protein phenotypes F, B. S I and $2, were less frequent among Eskimos. whereas genotypes, comprising any a l l e l e > n u m b e r 13 were more frequent. The median Lp(a) concentration in Eskimos (11.5 mg/dl) was significantly higher than in Caucasian Danes (6,33 mg/dl). W e conclude that other factors than apo(a) Kpni genntype determine Lp(a) concentrations in West Greenland Eskimos.
Serum lipoprotein(a) [Lp(a)] has been implicated in atherogenesis. Although case-control studies show higher Lp(a) levels in subjects with C H D , not all epidemiological studies support a causal rote in the disease. This conflict would be explained if Lp(a) is an acutephase protein, a role supported by the demonstration of functional interleukin-6 regulatory elements in the apo(a) gene promoter. High levels of activated macrophage products are found in the peritoneal fluid of women with endometriosis, a common disorder in which endometrial tissue is found outside of the lining of the uterine cavity. We studied 39 women with endometriosis and 39 healthy matched controls. Serum levels of lipid, lipoproteins and apolipoproteins were similar in the two groups, except for five-fold higher Lp(a) levels in w o m e n with endometriosis (median 15.0 mg/dl [range 0.05-87.3 mg/dl] vs. 3.0 mg/dl [0.05-29.0 mg/dl] in controls; P < 0 . O 0 1 ) . This loo difference remained highly significant after adjustment for differences in age, height, adiposity and Lp(a) 60[smoking. This study provides further evidence that Lp(a) is an (mg/dl) 40 -acute phase reactant and challenges the view that serum L p ( a ) l e v e l s 20 ~ will provide useful information _t 0 Cases Controls about a healthy individual's C H D (n=39) (n=39) risk.
Serum80I
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