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1.P.311 Apolipoprotein E polymorphism in healthy Argentine individuals
Monday 82
6 October 1997: Posters Genetic epidemiology
polymorphism consistent in the presence of 3 or 4 repeats of the tetranucleotide TGTC, already reported by von Eckardestein et al, 1992 (Am. .I. Hum. Genet. 50, 1115). Another polymorphic site, characterized by a Ser~hr change at residue 347 (Boerwinkle et al, 1990 Nut Acids Res. 18, 4996) creates a Hinfl site. The Hinfl allele was present with a frequency of 14%. We also found six unreported mutations at positions 557 (frequency 16%) 667 (lo%), 923 (27%), 1112 (27%), 1328 (25%) and 1696 (3%) according to the coordinates by Elshourbagy et al (1987, JBC 262, 7973). Three of them (557,667 and 1696) map within exons but they do not produce any change in the sequence of the protein. As they are not either in the regions responsible for the control of ApoAIV expression, they are not likely to be functionally important. However, because of their high frequency, they may be useful in the study of haplotypes of the ApoAI-CIII-AIV cluster.
I 1 .P
308
Age-dependent influence of some genes polymorphisms on predisposition to myocardii infarction in St. Petersburg, Russia
E.I. Schwartz, M.V. Volkova, A.M. Sverdlova, S.S. Baranovskaya, V.I. Vasina, E.V. Fomicheva. Petersburg Nuclear Physics Institute Petersburg area, Gatchina, 188350, Russia
RAS,
The purpose of our research was the comparative analysis of three genes’ alleles distribution - methylentetrahydrofolate reductase (MTHFR) Ala677Va1, factor V Leiden mutation and C/T +93 polymorphism of ape(a) gene among different age groups of myocardial infarction (MI) patients and control subjects. For this aim we have created the DNA banks from over 300 MI patients and 300 persons of control group. The analysis of genes structure was performed by PCR with following digestion by the appropriate restriction enzyme. We have not found any differences in all indicated genes alleles distribution between MI patients and the control group. However, the significant differences in Factor V Leiden and MTHFR Ala677Val alleles distribution were found between patients with MI after 60 years of age as compared to control subjects. In patients with MI before 55 years of age T allele has been presented with significant diminished frequency as compared to control group. Moreover, we have not obtained any MI patients bearing TT +93 ape(a) genotype. Our results allow us to make a conclusion that MTHFR Ala677Val and factor V Leiden mutation have the strong impact for predisposition to MI in the oldest group. On the other hand, we have detected the strong protective role of T +93 allele of ape(a) gene.
1 .P.309
Complement factor C3 genotype and risk of MI
J.W.B. Senaratne, L.A. Clark, CF. Terry, A. Hamsten, F.R. Green. NuJield Dept Surgery, University of Oxford, Oxford, UK; King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden The complement system is a cascade of plasma proteins that are activated by antibodies or cell surfaces to produce a membrane attack complex (mat) capable of cell lysis in response to microbial infection. Complement factor C3 is central to the cascade being at the convergence of the classical and alternative pathways of complement activation. Both the terminal (mat) and C3b, the part of C3 that catalyses formation of the mat, and the complex have been found in atherosclerotic plaques. Elevated plasma levels of C3 are associated prospectively with increased risk of MI and C3 itself is an acute-phase protein. C3 has two common polymorphisms, Rl02G and L314P, which are in strong but not complete linkage disequilibrium. The C3 102G allele, previously known as F (other allele S, for fast/slow electrophoretic migration), is associated with increased risk of atherosclerotic disease in various studies. We determined R102G genotype by PCR and HhaI digestion in a group of Swedish patients with MI before the age of 45 and age-matched controls. C3 RlOZG genotype
RR
RG
GG
COLltrOlS MI Cases
61 51
28 20
8 12
Neither genotype distribution nor allele frequency differed significantly between cases and controls. However there was a slight excess of GG homozygotes among cases, giving a relative risk for MI of 1.8 (95% CI 0.74.7). This, while not significant perhaps because of the small numbers involved, confirms previous observations in the literature for the F allele. It remains possible that C3 genotype may be involved in predisposition to atherosclerotic disease and merits exploration in larger studies perhaps with different endpoints. We acknowledge the British Heart Foundation and the Commonwealth Scholarship Commission. 11th International
Symposium
) 1. P.310
/
Apolipoprotein B signal peptide insertion/deletion polymorphism in hemodialysis patients
Mivahiko Sonobe’ , Motoshige Miyano’ , Osamu Nishiiwa’ , Takahiio Nishide’ , Iwao Nishide’ , Mituru Ozaki’ , Yoichi Yamada’ , Masatoshi Mune’ Keiji Mimura’ , Susumu Yukawa’ ‘Third Dept. of Znternal Med., Wahayama Med. Coil., Wakayama 640; ?Nishide Hosp., Kaizuka, Osaka 597, Japan We have investigated the insertion (Ins)/deletion (Del) polymorphism in the signal peptide region of the apo B gene in 56 chronic hemodialysis patients. The difference of nine nucleotides (93 bp, 84 bp) was detected using the polymerase chain reaction. We also examined whether this polymorphism is associated with accelerated atherosclerosis, evaluating the abdominal aortic calcification index (ACI) by computed tomography scan. The relative frequencies of Ins/Ins, Ins/Del, and Del/Del were 0.48, 0.36, and 0.16, respectively, which did not differ significantly when compared to the controls. In the case of Ins/Del, the serum levels of apo A-I and apo A-II were significantly higher than those of Ins/Ins or Del/Del. No significant differences among the 3 genotypes were observed in the levels of serum apo B, LDL-cholesterol, total cholesterol, triglycerides, or Lp(a). Ins&s had a slightly higher level of AC1 compared to Ins/Del or Del/Del, but this did not show a significant difference. The role of this polymorphism in lipid metabolism is unclear, however these results suggest that this polymorphism may influence lipid metabolism and accelerated atherosclerosis in hemodialysis patients indirectly through its effect on apo A-I and apo A-II metabolism.
1 1 .P.311
1 Apolipoprotein individuals
E polymorphism in healthy Argentine
P.B. Sorroche, S.B. Legal, S. Gutt, P.J. Brandi, J.M. Ohyamburu. Hospital Italian0 de Buenos Aires, Central Laboratory and Dept. of Nutrition, Buenos Aires, Argentina To asses the distribution of apolipoprotein E (apoE) polimorphism in Buenos Aires and their correlation with serum lipids, we studied 216 serum samples from blood donors, mainly Buenos Aires citizens, 131 men and 85 women aged 18-65 years old. This study is a preliminar and perhaps the first one on apoE phenotypes in Argentina. We measured total cholesterol in each sample by standard enzymatic procedures (Boehringer-Hitachi 717). ApoE phenotypes were analyzed by IEF followed by imrnunoblorting. Cholesterol values (mg/dl) are expresed as mean f SEM. For statistics we used the ANOVA one-way analysis of variance. The frequencies we found were E2l2 1.9% n = 4; E2l4 0.5% n = 1; E3l2 9.2% n = 20; E3l3 73.6% n = 159; E3l4 12.9% n = 28 and E4/4 1.9% n = 4, and the apoE allelic frequencies for ~2. ~3 and ~4, were 6.7%. 84.7% and 8.6% respectively. As in other Caucasians populations, the E3/3 was the most common phenotype. For apoE containing phenotypes (E3/2; E3/3; E3/4) the means of cholesterol were 186 f 6.9; 193 f 2.1 and 202 & 4.4, respectively. Test for linear trend between group means and group orders was significative (p = 0.04). This confirm the cholesterol trend to increase (~2 < ~3 < ~4) as was reported in the literature. Other phenotypes were not tested because of the small number of patients. Thanks to Grupo Bioquimico S.A. for financial assistence.
( 1 .P.312 ) Homocyst(e)me level but not MTHFR genotype predicts carotid atherosclerosis J.D. Snence, G. Sarquella-Brugada, G. Zhao, R. Brugada, R. Hegele, D. Freeman, M.R. Malinow. Robarts Research Rd, London, N6G 2V2. Canada
A.J. Marian, Inst., 1400 Western
We studied the relationship between plasma homocyst(e)ine, MTHFR genotype and carotid atherosclerosis measured as plaque area by 2-D ultrasound, in 351 volunteers and 438 patients from an Accelerated Atherosclerosis Clinic. Homocyst(e)ine [H(e)] measurements were done in 667 cases, and methylene-tetrahydrofolate reductase (MTHFR) genotypes in 307. For the overall population, Age was 49.3 & 12; Sex 53% male; Homocyst(e)ine levels were 13.4 i 8.2. MT-HFR genotype (C = normal, T = mutant)was CC in 124 (40.4%), CT in 143 (46%). ‘IT in 40 (13%): for those with nenotvoe, Aee was 51.7 + 11.4; Sex 52% male; H(e) level was: CC 12.5 + 5.9;~CT ly5 + 6.2; ‘IT 18.1 + 14 firnoliL (p < 0.0001); ‘PI H(e) level was Z-CC (p
on Atherosclerosis,
Paris, October
1997
,
6 October 1997: Posters Genetic epidemiology
polymorphism consistent in the presence of 3 or 4 repeats of the tetranucleotide TGTC, already reported by von Eckardestein et al, 1992 (Am. .I. Hum. Genet. 50, 1115). Another polymorphic site, characterized by a Ser~hr change at residue 347 (Boerwinkle et al, 1990 Nut Acids Res. 18, 4996) creates a Hinfl site. The Hinfl allele was present with a frequency of 14%. We also found six unreported mutations at positions 557 (frequency 16%) 667 (lo%), 923 (27%), 1112 (27%), 1328 (25%) and 1696 (3%) according to the coordinates by Elshourbagy et al (1987, JBC 262, 7973). Three of them (557,667 and 1696) map within exons but they do not produce any change in the sequence of the protein. As they are not either in the regions responsible for the control of ApoAIV expression, they are not likely to be functionally important. However, because of their high frequency, they may be useful in the study of haplotypes of the ApoAI-CIII-AIV cluster.
I 1 .P
308
Age-dependent influence of some genes polymorphisms on predisposition to myocardii infarction in St. Petersburg, Russia
E.I. Schwartz, M.V. Volkova, A.M. Sverdlova, S.S. Baranovskaya, V.I. Vasina, E.V. Fomicheva. Petersburg Nuclear Physics Institute Petersburg area, Gatchina, 188350, Russia
RAS,
The purpose of our research was the comparative analysis of three genes’ alleles distribution - methylentetrahydrofolate reductase (MTHFR) Ala677Va1, factor V Leiden mutation and C/T +93 polymorphism of ape(a) gene among different age groups of myocardial infarction (MI) patients and control subjects. For this aim we have created the DNA banks from over 300 MI patients and 300 persons of control group. The analysis of genes structure was performed by PCR with following digestion by the appropriate restriction enzyme. We have not found any differences in all indicated genes alleles distribution between MI patients and the control group. However, the significant differences in Factor V Leiden and MTHFR Ala677Val alleles distribution were found between patients with MI after 60 years of age as compared to control subjects. In patients with MI before 55 years of age T allele has been presented with significant diminished frequency as compared to control group. Moreover, we have not obtained any MI patients bearing TT +93 ape(a) genotype. Our results allow us to make a conclusion that MTHFR Ala677Val and factor V Leiden mutation have the strong impact for predisposition to MI in the oldest group. On the other hand, we have detected the strong protective role of T +93 allele of ape(a) gene.
1 .P.309
Complement factor C3 genotype and risk of MI
J.W.B. Senaratne, L.A. Clark, CF. Terry, A. Hamsten, F.R. Green. NuJield Dept Surgery, University of Oxford, Oxford, UK; King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden The complement system is a cascade of plasma proteins that are activated by antibodies or cell surfaces to produce a membrane attack complex (mat) capable of cell lysis in response to microbial infection. Complement factor C3 is central to the cascade being at the convergence of the classical and alternative pathways of complement activation. Both the terminal (mat) and C3b, the part of C3 that catalyses formation of the mat, and the complex have been found in atherosclerotic plaques. Elevated plasma levels of C3 are associated prospectively with increased risk of MI and C3 itself is an acute-phase protein. C3 has two common polymorphisms, Rl02G and L314P, which are in strong but not complete linkage disequilibrium. The C3 102G allele, previously known as F (other allele S, for fast/slow electrophoretic migration), is associated with increased risk of atherosclerotic disease in various studies. We determined R102G genotype by PCR and HhaI digestion in a group of Swedish patients with MI before the age of 45 and age-matched controls. C3 RlOZG genotype
RR
RG
GG
COLltrOlS MI Cases
61 51
28 20
8 12
Neither genotype distribution nor allele frequency differed significantly between cases and controls. However there was a slight excess of GG homozygotes among cases, giving a relative risk for MI of 1.8 (95% CI 0.74.7). This, while not significant perhaps because of the small numbers involved, confirms previous observations in the literature for the F allele. It remains possible that C3 genotype may be involved in predisposition to atherosclerotic disease and merits exploration in larger studies perhaps with different endpoints. We acknowledge the British Heart Foundation and the Commonwealth Scholarship Commission. 11th International
Symposium
) 1. P.310
/
Apolipoprotein B signal peptide insertion/deletion polymorphism in hemodialysis patients
Mivahiko Sonobe’ , Motoshige Miyano’ , Osamu Nishiiwa’ , Takahiio Nishide’ , Iwao Nishide’ , Mituru Ozaki’ , Yoichi Yamada’ , Masatoshi Mune’ Keiji Mimura’ , Susumu Yukawa’ ‘Third Dept. of Znternal Med., Wahayama Med. Coil., Wakayama 640; ?Nishide Hosp., Kaizuka, Osaka 597, Japan We have investigated the insertion (Ins)/deletion (Del) polymorphism in the signal peptide region of the apo B gene in 56 chronic hemodialysis patients. The difference of nine nucleotides (93 bp, 84 bp) was detected using the polymerase chain reaction. We also examined whether this polymorphism is associated with accelerated atherosclerosis, evaluating the abdominal aortic calcification index (ACI) by computed tomography scan. The relative frequencies of Ins/Ins, Ins/Del, and Del/Del were 0.48, 0.36, and 0.16, respectively, which did not differ significantly when compared to the controls. In the case of Ins/Del, the serum levels of apo A-I and apo A-II were significantly higher than those of Ins/Ins or Del/Del. No significant differences among the 3 genotypes were observed in the levels of serum apo B, LDL-cholesterol, total cholesterol, triglycerides, or Lp(a). Ins&s had a slightly higher level of AC1 compared to Ins/Del or Del/Del, but this did not show a significant difference. The role of this polymorphism in lipid metabolism is unclear, however these results suggest that this polymorphism may influence lipid metabolism and accelerated atherosclerosis in hemodialysis patients indirectly through its effect on apo A-I and apo A-II metabolism.
1 1 .P.311
1 Apolipoprotein individuals
E polymorphism in healthy Argentine
P.B. Sorroche, S.B. Legal, S. Gutt, P.J. Brandi, J.M. Ohyamburu. Hospital Italian0 de Buenos Aires, Central Laboratory and Dept. of Nutrition, Buenos Aires, Argentina To asses the distribution of apolipoprotein E (apoE) polimorphism in Buenos Aires and their correlation with serum lipids, we studied 216 serum samples from blood donors, mainly Buenos Aires citizens, 131 men and 85 women aged 18-65 years old. This study is a preliminar and perhaps the first one on apoE phenotypes in Argentina. We measured total cholesterol in each sample by standard enzymatic procedures (Boehringer-Hitachi 717). ApoE phenotypes were analyzed by IEF followed by imrnunoblorting. Cholesterol values (mg/dl) are expresed as mean f SEM. For statistics we used the ANOVA one-way analysis of variance. The frequencies we found were E2l2 1.9% n = 4; E2l4 0.5% n = 1; E3l2 9.2% n = 20; E3l3 73.6% n = 159; E3l4 12.9% n = 28 and E4/4 1.9% n = 4, and the apoE allelic frequencies for ~2. ~3 and ~4, were 6.7%. 84.7% and 8.6% respectively. As in other Caucasians populations, the E3/3 was the most common phenotype. For apoE containing phenotypes (E3/2; E3/3; E3/4) the means of cholesterol were 186 f 6.9; 193 f 2.1 and 202 & 4.4, respectively. Test for linear trend between group means and group orders was significative (p = 0.04). This confirm the cholesterol trend to increase (~2 < ~3 < ~4) as was reported in the literature. Other phenotypes were not tested because of the small number of patients. Thanks to Grupo Bioquimico S.A. for financial assistence.
( 1 .P.312 ) Homocyst(e)me level but not MTHFR genotype predicts carotid atherosclerosis J.D. Snence, G. Sarquella-Brugada, G. Zhao, R. Brugada, R. Hegele, D. Freeman, M.R. Malinow. Robarts Research Rd, London, N6G 2V2. Canada
A.J. Marian, Inst., 1400 Western
We studied the relationship between plasma homocyst(e)ine, MTHFR genotype and carotid atherosclerosis measured as plaque area by 2-D ultrasound, in 351 volunteers and 438 patients from an Accelerated Atherosclerosis Clinic. Homocyst(e)ine [H(e)] measurements were done in 667 cases, and methylene-tetrahydrofolate reductase (MTHFR) genotypes in 307. For the overall population, Age was 49.3 & 12; Sex 53% male; Homocyst(e)ine levels were 13.4 i 8.2. MT-HFR genotype (C = normal, T = mutant)was CC in 124 (40.4%), CT in 143 (46%). ‘IT in 40 (13%): for those with nenotvoe, Aee was 51.7 + 11.4; Sex 52% male; H(e) level was: CC 12.5 + 5.9;~CT ly5 + 6.2; ‘IT 18.1 + 14 firnoliL (p < 0.0001); ‘PI H(e) level was Z-CC (p
on Atherosclerosis,
Paris, October
1997
,