Optimization of laboratory workflow in clinical hematology laboratory with reduced manual slide review: comparison between Sysmex XE-2100 and ABX Pentra DX120.

INTRODUCTION: The validation of automated hematology analyzer results by manual slide review (MSR) is currently an inevitable work process in clinical hematology laboratories. The laboratory workload would be optimized if the requirement for MSR could be reduced without compromising patient care. We investigated whether slide-making rates would be different between two hematology analyzers, which were paired with their own automated slide makers/stainers: Sysmex XE-2100 with SP-1000i (Sysmex, Kobe, Japan) and ABX Pentra DX120 with SPS evolution (ABX-Horiba, Montpellier, France). METHODS: A total of 943 samples were run in parallel on the Sysmex XE-2100 and ABX Pentra DX120. Reflex slides were automatically made in each analyzer according to its own criteria, which reflected the criteria of MSR in our laboratory. The slide-making rates were compared, and the results were further confirmed using the criteria of MSR. RESULTS: The slide-making rates in Sysmex XE-2100, ABX Pentra DX120, and manual review were 22.5% (212/943), 15.91% (150/943), and 11.5% (108/943), respectively. In 774 (82.1%) samples, the three methods showed concordant results, and all made slides in 82 samples. Using the manual method as a standard, the sensitivity and specificity were 86.1% and 85.8% in Sysmex XE-2100 and 89.8% and 93.7% in ABX Pentra DX120. CONCLUSION: Our data show that the slide-making rates are variable in different hematology analyzers. It also implies that although MSR cannot be fully substituted by modern hematology analyzers, it can be effectively reduced to optimize laboratory workload.

Haptoglobin genotypic distribution (including Hp0 allele) and associated serum haptoglobin concentrations in Koreans.

BACKGROUND: Haptoglobin polymorphism is associated with the prevalence of infections, autoimmune diseases, cardiovascular diseases, and other disorders. Congenital haptoglobin deficiency is associated with anaphylactic transfusion reactions in anhaptoglobinaemic patients with antihaptoglobin antibody. AIMS: To investigate haptoglobin genotypic distribution (including the Hp(0) allele) and associated serum haptoglobin concentrations in Koreans. METHODS: Five hundred and nine healthy Korean adults were randomly selected. Two methods were used: haptoglobin genotyping based on a polymerase chain reaction (PCR) system that exploited the structural difference of the Hp(1) and Hp(2 )alleles, and another PCR method that detected haptoglobin gene deletion by amplification of the junctional region of the Hp(0) allele. Serum haptoglobin concentrations were measured by nephelometry. RESULTS: The haptoglobin genotypes of 509 subjects were as follows: Hp(1)Hp(1), 7.1%; Hp(2)Hp(1), 37.7%; Hp(2)Hp(2), 49.3%; Hp(0)Hp(1), 2.2%; Hp(0)Hp(2), 3.5%; Hp(0)Hp(0), 0.2%. The gene frequency of Hp(0) in Koreans was calculated to be 0.031. Significant differences were seen among the concentrations of each haptoglobin genotype (Kruskal-Wallis test). Hp(0)Hp(2), but not Hp(0)Hp(1), was associated with hypohaptoglobinaemia. CONCLUSIONS: PCR methods for differentiating between haptoglobin genotypes, including the Hp(0) allele, may be useful in a broad spectrum of basic studies and clinical examinations.

The haplotype analyses using multiple markers of the apolipoprotein B gene in patients with coronary artery disease.

The high level of low density lipoprotein (LDL) is a risk factor for cardiovascular disease. Apolipoprotein (apo) B is a major protein component of LDL and plays an important role in the maintenance of cholesterol homeostasis. In this study, six polymorphic sites of the apoB gene were anlaysed in 235 patients with coronary artery disease (CAD) and 216 normal control subjects. There were no significant differences in the allele frequencies of apoB polymorphisms between the control and patient groups. However, haplotype frequencies were significantly different between the CAD patients and control (p<0.05). In addition, the allelic distributions of both EcoRI and MspI polymorphisms in Koreans were similar to those in Chinese but significantly different from those in Caucasians. ApoB polymorphisms showed no association with plasma lipid levels. In conclusion, haplotype analysis of the apoB gene using multiple diallelic markers might be a useful marker for Korean CAD patients.

Studies on the plasma lipid profiles, and LCAT and CETP activities according to hyperlipoproteinemia phenotypes (HLP).

Hyperlipoproteinemia phenotypes (HLP), one of genetic disorders with an estimated prevalence of 0.5-2% in the general population, is responsible for 10% of premature CHD. After first screening with the high cholesterol (>6.47 mM/l) and triglyceride (TG) (>2.6 mM/l) levels without medication, subjects were typed for HLP classification. Differential metabolic effects of HLP types on plasma lipid profiles and the reverse cholesterol transport system (RCT) were studied in 196 HLP types (91.2%) and 19 non-HLP (8.8%). A total of 45% of subjects had primary HLP and the others had NIDDM (10.7%), hypertension (9.3%) and other chronic diseases. Type IV HLP (58.6%) was most predominant and Types IIa, IIb, III and V comprised 16.7, 12.1, 2.3 and 1.4% of the HLP. Type I was not found. Plasma lipids excluding apo A-I and Lp(a) were significantly different among HLP compared to non-HLP (P<0.001). Since Type V and III impact the clearance of TG-riched lipoproteins, TG and VLDL-C levels were higher in V and III. TG and LDL-C were higher in Type II than those in the others because of defect of LDL receptors. LCAT activity, lower in Type III and Type IV and highest in Type V, was highly associated with plasma free cholesterol levels and the ratio of apoB/apoA and LDL/HDL. CETP activity was highest in Type V due to high VLDL-C and TG and low HDL-C. The ratio of LCAT/CETP was not different among HLP types but was significantly lower in HLP than in non-HLP. CETP increased 2-3 times as well as LCAT decreased among HLP patients compared to non-HLP. We conclude non-HLP subjects with high cholesterol and TG levels do not always mean high risk of CHD and the intervention effects of HLP types would lead to impose the risk of CHD by the impact of RCT.

Genetic variations of the paraoxonase gene in patients with coronary artery disease.

OBJECTIVES: Paraoxonase (PON) plays an important role in preventing low density lipoprotein (LDL) oxidation and thus may be involved in protection against atherosclerosis. Several studies have suggested that genetic variations of the PON gene are associated with plasma HDL levels and coronary artery disease (CAD). This study was conducted to elucidate the association between three polymorphisms of the PON1 and PON2 genes and Korean patients with CAD. DESIGN AND METHODS: One hundred ninety-one patients with CAD and 113 age-matched normal controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for PON polymorphisms by restriction enzyme digestion. RESULTS: There was linkage disequilibria between each polymorphism pair in the CAD and control groups. The Hsp92II polymorphism at codon 54 of the PON1 gene was positively associated with HDL-cholesterol levels in the control group (p = 0.02). An association between the AlwI polymorphism and HDL-cholesterol level appeared statistically significant in women of the normal group (p = 0.04). In addition, the DdeI and AlwI polymorphisms were positively associated with HDL (p = 0.02) and LDL (p = 0.03) levels in men of the CAD group, respectively. CONCLUSIONS: Our study suggested a gene-gene interaction between the PON1 and PON2 polymorphisms for CAD risk. However, we could not exclude the possibility that these polymorphisms may have linkage disequilibrium with a tightly linked PON3 locus or significant atherosclerotic alleles of nearby genes. Family studies may, therefore, help to confirm the role of the PON polymorphism for CAD risk.

Genetic variation of the methylenetetrahydrofolate reductase and cystathionine beta-synthase genes in Korean patients with coronary artery disease and a new polymorphism in intron 7.

We investigated polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes in Korean patients with coronary artery disease (CAD) and identified a new polymorphism (c-->t) in intron 7 of the CBS gene using the single-strand conformation polymorphism method. No significant differences were found in allele frequencies for either gene between the CAD and normal groups although the frequency of the so-called thermolabile MTHFR polymorphism, a proposed risk factor for CAD, was higher in Koreans than in other populations studied. The relatively low incidence of CAD in Korea suggests that this MTHFR polymorphism is not causative in this population.

Apolipoprotein E polymorphism and serum lipoprotein(a) concentrations in a Korean male population.

The purpose of this study was to investigate the effect of apolipoprotein E polymorphism on lipoprotein(a) metabolism by comparing serum lipoprotein(a) concentration with apolipoprotein E genotype in a Korean male population whose high molecular weight (HMW) lipoprotein(a) frequency was 95-98%. Serum lipoprotein(a), total cholesterol, triglyceride and high-density lipoprotein-cholesterol concentrations were measured and the apolipoprotein E genotype determined in 1189 healthy Korean males. The medians of serum lipoprotein(a) concentration in the apo E 2/3 group (0.105 g/L) and the apo E 3/4 group (0-116 g/L) were significantly lower than that in the apo E 3/3 group (0.155 g/L; P < 0.001). The medians of serum triglyceride were 1.497 mmol/L in the apo E 2/3 group, 1.356 mmol/L in the apo E 3/4 group, and 1.452 mmol/L in the apo E 3/3 group (P<0.05). With the significant difference in the serum lipoprotein(a) concentration in Korean males according to apolipoprotein E genotype, and with the negative correlation between serum triglyceride concentration and serum lipoprotein(a) concentration, it is suggested that apolipoprotein E polymorphism and serum triglyceride participate in the metabolism of lipoprotein(a) with HMW.

Genetic variations of cholesterol ester transfer protein gene in Koreans.

An absence of cholesterol ester transfer protein (CETP, protein; CETP, gene) results in an increase of the apolipoprotein AI levels and a decrease in the low density lipoprotein (LDL) levels. Thus, the CETP polymorphism is important in the assessment of risk of atherosclerosis. This study was conducted to elucidate the genotype distributions of the CETP polymorphism and association with plasma lipid levels in Koreans. The genotypes of the TaqI A and B polymorphic loci were associated with plasma triglyceride levels in the control and coronary artery disease (CAD) groups. There was linkage disequilibrium between TaqI A and B loci in the control group (chi2 = 5.58, p < 0.05). Association studies of the CETP polymorphism have been carried out mainly with Caucasian populations; however, the results have not been consistent among different populations. A possible explanation for this diversity among populations may be differences in genetic backgrounds, which may be more important than environmental factors. We discuss the reasons for the incompatibility of the CETP polymorphism among populations.

Association between triglyceride-rich lipoprotein remnant receptor polymorphisms and lipid traits.

OBJECTIVES: The metabolism of triglyceride-rich lipoproteins (TRL) is, in part, mediated by lipoprotein receptors (such as low density lipoprotein receptor-related protein [LRP] and very low density lipoprotein [VLDL] receptors), which recognize TRL remnants after specific binding with apolipoprotein E. The purpose of this study was to explore the association of the genetic polymorphisms of remnant receptors with lipid, lipoprotein, and apolipoprotein levels including remnant-like particle-cholesterol (RLP-C). DESIGN AND METHODS: Using polymerase chain reaction-amplified DNA, VLDL receptor tetranucleotide repeat polymorphism, LRP trinucleotide repeat polymorphism, and LRP exon 3 polymorphism were analyzed in normal adults (control group: n = 161) and in patients with coronary artery disease (CAD group: n = 102). RESULTS: The allelic distributions of VLDL receptor triple repeat polymorphism, LRP tetranucleotide repeat polymorphism, and LRP exon 3 polymorphism in Koreans were similar to those of Japanese but were significantly different from those of other ethnic groups. There were no significant differences in the allele frequencies of the polymorphisms between the control and CAD groups. VLDL receptor polymorphism in the control group (p = 0.0403) and LRP exon 3 polymorphism in the CAD group (p = 0.0459) showed significant associations with lipoprotein (a) [Lp(a)] levels. CONCLUSIONS: The results of the present study demonstrated significant interracial distribution of remnant receptor polymorphisms. There was no association between the remnant receptor polymorphisms and the RLP-C levels. However, the polymorphisms showed a significant association with Lp(a), which may suggest that the Lp(a) metabolism is in part mediated by the uptake through the remnant receptors.

Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease.

BACKGROUND: Plasma NOx (nitrate and nitrite) is a stable end product of the vasodilator NO. Several polymorphisms in the endothelial constitutive NO synthase (ecNOS) gene have been reported, including the 4a/4b VNTR polymorphism in intron 4, the E298D mutation in exon 7, and the G10-T polymorphism in intron 23. The aims of this study were to examine plasma NOx in patients with coronary artery disease (CAD) and to assess the association between plasma NOx concentrations and the three ecNOS gene polymorphisms. METHODS: Plasma NOx was measured in samples from 128 healthy controls and from 110 CAD patients at least 2 months after myocardial infarction. Three genetic polymorphisms that are known or have been suggested to be associated with plasma NOx concentration were also analyzed by PCR-restriction fragment length polymorphism. RESULTS: Median plasma NOx was significantly higher (P <0.001) in CAD patients (95.9 micromol/L) than in controls (73.8 micromol/L). Furthermore, the median plasma NOx was significantly higher (P <0.001) in hypertensive CAD patients (116.0 micromol/L) than in controls and normotensive CAD patients (86.0 micromol/L). The G-allele frequency of the G10-T polymorphism in intron 23 was significantly higher in CAD patients than in controls. Other polymorphisms showed no differences in allelic frequencies among the control and CAD groups. In controls, individuals with the E298D mutation in exon 7 (136.1 micromol/L) showed significantly higher (P = 0.001) median plasma NOx than those without this mutation (64.5 micromol/L). CONCLUSIONS: Plasma NOx was higher in hypertensive CAD patients than in normotensive CAD patients and controls. The E298D polymorphism of the ecNOS gene was associated with increased plasma NOx. Further study is needed to understand the gene expression and enzyme activity of ecNOS and their association with genotypes.

Remnant-like particle cholesterol levels in Korean patients with coronary artery disease and non-insulin dependent diabetes mellitus.

Several studies have provided evidence that the remnants of lipoproteins may be the atherogenic components of triglyceride-rich lipoproteins. The purpose of this study was to investigate whether the remnant-like particle cholesterol (RLP-C) is an independent risk factor for coronary artery disease (CAD) and non-insulin dependent diabetes mellitus (NIDDM) in the Korean population and to explore the relationship between RLP-C and other biochemical markers as well as the apolipoprotein (apo) E genotypes. Lipid and lipoproteins including RLP-C and apo E genotypes were analyzed in 98 normal adults (control group), 68 patients with CAD (CAD group), 88 patients with NIDDM (DM group), and 19 patients with both CAD and NDDM (CAD + DM group). RLP-C levels were significantly higher in the DM (p < 0.0001), CAD (p = 0.0012) and the CAD + DM groups (p = 0.0184) than in the controls. To determine which variable could discriminate most effectively and independently among the different groups, stepwise linear discriminant analysis was performed for all the variables that showed p < 0.15 by univariate analysis. RLP-C was selected as an independent discriminator between the control and patient groups. RLP-C levels showed a strong positive correlation with trigylceride levels in the control, CAD and DM groups (r = 0.783, r = 0.610 and r = 0.746, respectively). In overall groups, apo epsilon4 and epsilon2 carrier genotypes showed a significant increase in RLP-C levels compared with epsilon3/3 wild-type (p = 0.0085). After adjusting for the effect of apo E genotypes, a significant increase of the RLP-C levels in the disease groups remained. In conclusion, RLP-C was determined to be an independent risk factor in Korean patients with CAD and NIDDM and showed a strong correlation with triglyceride levels. We suggest that the increased cardiovascular risk associated with the epsilon4 and epsilon2 allele may be mediated by more atherogenic RLP-C.

Genetic variations of the hepatic lipase gene in Korean patients with coronary artery disease.

OBJECTIVES: To investigate the association between the HL gene (LIPC) polymorphism, plasma lipid levels and coronary artery disease (CAD). DESIGN AND METHODS: One hundred thirty-seven subjects with CAD and 124 age-matched controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for LIPC genotyping by enzyme digestion. RESULTS: The allele frequencies of the three polymorphisms in the LIPC gene were not significantly different between the controls and CAD patients. The + allele of the -514 promoter polymorphism was associated with higher total cholesterol (p = 0.05), apolipoprotein (apo) AI (p = 0.04) levels in the men of the normal group, and the apoB level (p = 0.03) in the women of the CAD group without allele effect. The allele frequencies of the -250 and -514 promoter polymorphisms of Koreans were significantly different from those of the white and African American populations studied (p < 0.05). CONCLUSIONS: The -514 promoter polymorphism may fluctuate on the lipid levels due to linkage disequilibria with other polymorphisms of the LIPC gene or nearby genes. The difference of the -250 promoter allele frequencies among the different populations may partially explain the variation of the HDL levels in ethnic groups. To elucidate the more exact associations of LIPC polymorphism with the plasma lipid levels, the precise biochemical mechanisms of the LIPC alleles are required.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and coagulation factor VII Arg353-->Gln polymorphism in Korean patients with coronary artery disease.

An increased risk for arterial thrombosis is associated with high plasma levels of coagulation and fibrinolytic factors such as PAI-1 and FVII. In this study, the 4G/5G polymorphism in the promoter of PAI-1 gene and Arg353-->Gln polymorphism in the FVII gene were analysed in 139 normal adults and 158 patients with coronary artery disease (CAD), and their association with plasma lipid traits was investigated. There were no significant differences in the allele frequencies of PAI-1 and FVII polymorphisms between control and patient groups. The allelic distributions of both polymorphisms in Koreans were similar to those in Japanese but significantly different from those in Caucasians. In the CAD group, the 4G homozygotes of PAI-1 polymorphism showed significantly higher levels of total (p=0.0250) and LDL cholesterol (p=0.0335) with individuals having other genotypes. However, FVII polymorphism showed no association with lipid levels. In conclusion, the 4G/5G PAI-1 promoter polymorphism and Arg353-->Gln FVII polymorphism are not major genetic risk factors for CAD in Koreans. However, 4G allele of PAI-1 polymorphism revealed to be associated with the levels of cholesterol, especially LDL cholesterol levels in CAD patients.

Distribution of haptoglobin phenotypes in a Korean population, using the semi-automated PhastSystem.

We have established a new phenotyping method for haptoglobin, based on sodium dodecyl sulphate-polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia Biotech, Uppsala, Sweden), followed by immunoblotting for detection. We measured haptoglobin concentrations and determined the haptoglobin phenotypes of 316 healthy Koreans using this method: 31 (9.8%) were of Hp 1-1 type, 140 (44.3%) of Hp 2-1 type and 145 (45.9%) of Hp 2-2 type. The haptoglobin allele frequencies were calculated to be 0.32 for Hp1 and 0.68 for Hp2. We were able to visualize up to 12 bands from the human Hp 2-2 polymeric series, with molecular weights in the range 171.9 x 10(3) to 802.2 x 10(3). The reference range of serum haptoglobin concentrations obtained by the IFCC (International Federation of Clinical Chemistry) standard method was 0.27-2.14 g/L. The serum haptoglobin concentration in Koreans was similar to that of Caucasians, but the Hp1 allele frequency was lower in Koreans. Our method could be used in clinical laboratories as a simple and practical method of haptoglobin phenotyping. In addition, the Hp 2-2 polymeric series could be used as high molecular weight standards.

Fibrinogen gene polymorphism in a non-Caucasian population.

OBJECTIVE: The purpose of this study was to investigate the two polymorphisms of fibrinogen gene (RsaI and MnlI RFLPs in the coding region of the fibrinogen gene) in Koreans, and their relation to plasma fibrinogen. METHODS: Using PCR-amplified DNAs, RsaI and MnlI RFLPs were analyzed in 112 patients with coronary artery disease (CAD) and 137 healthy subjects. To compare the mean of plasma fibrinogen and lipid levels among different genotypes, one-way analysis of variance (ANOVA) test was performed. RESULTS: Allele frequencies of fibrinogen gene polymorphism in Koreans were not significantly different between CAD and control groups; fibrinogen polymorphism in this population showed a lack of association with plasma fibrinogen levels, but significant association with BMI (p < 0.05). CONCLUSION: This evidence suggests that in Korean populations, fibrinogen gene polymorphism is not a factor in the expression of atherosclerosis. There might, however, be an association between fibrinogen gene and obesity in such population.

The risk groups for coronary heart disease in Koreans. Assessment by distribution of serum lipid concentrations.

Coronary heart disease is the most severe form of disease caused by atherosclerosis; and there is a strong relationship between serum lipid concentrations and atherosclerosis. By decade of life, means, standard deviations and selected percentiles were calculated according to sex for serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride in 69,563 Koreans. The prevalence of dyslipoproteinemias which were related to high risk of coronary heart disease were assessed. The mean concentrations of serum total cholesterol and LDL-C in the Korean population were 5.02 mmol/l and 3.00 mmol/l. The 75th and 90th percentile concentrations of total cholesterol were 5.59 mmol/l and 6.24 mmol/l. The mean concentrations of serum triglyceride and HDL-C were 1.58 mmol/l and 1.30 mmol/l. The hyperlipoproteinemia type IV (4.8%) was the most frequent, followed by Type IIa (4.6%), hypoalphalipoproteinemia (3.3%), and type IIb (0.2%). According to the National Cholesterol Education Program Adult Treatment Panel II, 4.1% of Korean adults needed the initial drug therapy and 10.8% the initial dietary therapy for hypercholesterolemia. The age and sex-specific treatment guidelines for hypercholesterolemia would make it possible that early intervention could be applied to atherosclerosis in Korean adults.

Association between apolipoprotein(a) polymorphism and Lp(a) levels in Koreans.

In view of the clinical importance of lipoprotein(a) [(Lp(a)] in coronary artery disease (CAD), we investigated the apo(a) size polymorphism, sequence polymorphisms of five base repeats [(TTTTA)n] in the noncoding region, and of Met/Thr in the coding region of the apolipoprotein(a) [apo(a)] gene. The apo(a) polymorphisms were examined in 184 Korean patients with CAD and 121 healthy subjects. In size polymorphism, there was an inverse association between plasma Lp(a) levels and the apo(a) isoforms in the CAD group (p < 0.005). For (TTTTA)n sequence polymorphism, subjects with the 8/8 genotype were most frequently observed in the two groups. Plasma Lp(a) levels showed a significant difference between the 8/5 versus the 8/8 genotype in the CAD group. On the other hand, Lp(a) levels varied significantly among the genotypes of a Met/Thr polymorphism in normal controls (P < 0.01). The heterozygous genotype had an intermediate level of Lp(a) between the two homozygous genotypes, thereby showing gene dosage effect. Thus, it is possible that the apo(a) polymorphisms are responsible for variations in the Lp(a) levels.

Linkage disequilibrium of the Apo AI-CIII-AIV gene cluster and their relationship to plasma triglyceride, apolipoprotein AI and CIII levels in Koreans.

More than 20 different RFLPs have been described in the apo AI-CIII-AVI gene cluster and their association with several dyslipidemias has been claimed in different populations. So far, however, the results of their association have been largely inconclusive. We analyzed six previously described RFLPs (Paul-Hayase et al., 1992) in the apo AI-CII-AIV gene cluster by using PCR-amplified DNAs in 132 healthy subjects to document the relationship between the RFLPs and dyslipoproteinemias. The polymorphic sites were located in the promoter region of the apo AI gene (G to A substitution, MspI), in the 3' flanking region of the apo AI gene (PstI), in the 3' noncoding region of the apo CIII gene (SstI), in the first intron of the apo CIII gene (PvuIIa), in the intergenic region of the apo CIII and apo AIV genes (PvuIIb), and in the second intron of the apo AIV gene (XbaI), respectively. The allele frequencies of PstI polymorphism showed no ethnic difference. However, in G to A substitution sites (MspI), Koreans had a lower G allele frequency than that of Caucasians. Among Oriental ethnic groups there were no significant differences in the allele frequencies of SstI and PvuIIa RFLPs, whereas significant differences existed between individuals of Oriental, Caucasian, and/or African origins. Koreans were monomorphic for PvuIIb and XbaI restriction sites. Pairwise linkage disequilibrium analysis revealed two pairs of significant negative linkage disequilibriums (MspI-SstI and SstI-PvuIIa). Although there were no statistical significances, the S2 allele of SstI polymorphism and the G allele of MspI polymorphism seemed to be associated with hypertriglyceridemia. Thus linkage of the G allele of MspI polymorphism and the S2 allele of SstI polymorphism could give an additive effect on an increment of triglyceride levels. We did not find any association between the SstI polymorphism and apo CIII levels. In conclusion, there were no statistically significant relationships detected between the apo AI-CIII-AVI gene cluster polymorphisms and the levels of various lipid parameters.

Molecular bases of coronary heart disease in Koreans.

Coronary heart disease (CHD) has been considered as a multifactorial disorder with the involvement of both environmental and genetic factors. The advent of tools to investigate individual variability of DNA has allowed us to perform the association studies of candidate genes. However, an association between genetic trait and phenotypic variations is not easy to demonstrate and several reported association between genetic markers and risk factors or overt CHD have gone unconfirmed. It should not be assumed that for a given genetic trait, the impact on risk will be similar in all populations. In particular, most studies of the molecular bases of CHD have involved Caucasian subjects, so much more work with the Korean population is needed before genetic testing for susceptibility to CHD can be offered to Koreans as a clinical service. In this review, we discuss two aspects of the molecular bases of CHD: i) Molecular bases of the candidate gene related to lipoprotein metabolism including apolipoprotein AI-CIII-AIV gene duster, apolipoprotein B, apolipoprotein E-CI-CII gene cluster, apolipoprotein(a), LDL receptors, lipoprotein lipase, cholesteryl ester transfer protein, and apo B editing protein; ii) Molecular bases of the candidate gene related to thrombotic and other factors including fibrinogen, factor VII, plasminogen activator inhibitor 1, homocysteine, stromelysin, paraoxonase, and angiotensin converting enzyme. Studies involving the Korean population, especially those performed by our teams, are also summarized.