Genetic Polymorphisms In Patients Research Articles

CYP17 genetic polymorphism in patients with endometrial hyperplasia and cancer

We investigated the association of CYP17 gene polymorphism with the risk of having endometrial cancer and a well-known precursor of it, endometrial hyperplasia. Group A (control group) consisted of 35 patients who had histologically proven normal endometrium. Group B and C consisted of 18 and 30 patients who had endometrial hyperplasia with and without atypia, respectively. Group D consisted of 57 patients who had endometrial cancer. Venous blood samples were collected from patients in groups, and polymerase chain reaction was performed to determine the CYP17 gene polymorphism. Significant increase of A1/A1 and a decrease of A1/A2 genotype frequencies have been determined in patients with endometrial cancer and with atypical endometrial hyperplasia. No significant differences were found between groups in the frequency of A2/A2 genotype. There was no significant difference between the groups in the meaning of allele distributions. CYP17 polymorphism had correlation with endometrial atypia and cancer. Related effects of different types of CYP17 gene variants on the progression of hyperplastic endometrial cells into carcinoma should be evaluated in further studies. Progress in this area would help us modulate preventive treatments used in those actual high-risk group patients.

CYP17 genetic polymorphism in patients with endometrial hyperplasia and cancer

We investigated the association of CYP17 gene polymorphism with the risk of having endometrial cancer and a well-known precursor of it, endometrial hyperplasia. Group A (control group) consisted of 35 patients who had histologically proven normal endometrium. Group B and C consisted of 18 and 30 patients who had endometrial hyperplasia with and without atypia, respectively. Group D consisted of 57 patients who had endometrial cancer. Venous blood samples were collected from patients in groups, and polymerase chain reaction was performed to determine the CYP17 gene polymorphism. Significant increase of A1/A1 and a decrease of A1/A2 genotype frequencies have been determined in patients with endometrial cancer and with atypical endometrial hyperplasia. No significant differences were found between groups in the frequency of A2/A2 genotype. There was no significant difference between the groups in the meaning of allele distributions. CYP17 polymorphism had correlation with endometrial atypia and cancer. Related effects of different types of CYP17 gene variants on the progression of hyperplastic endometrial cells into carcinoma should be evaluated in further studies. Progress in this area would help us modulate preventive treatments used in those actual high–risk group patients.

Genetic Polymorphisms in Patients with Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.

Associations Between Drug Metabolism Genotype, Chemotherapy Pharmacokinetics, and Overall Survival in Patients With Breast Cancer

To evaluate associations between patient survival, pharmacokinetics, and drug metabolism-related genetic polymorphisms in patients receiving a combination chemotherapy regimen for breast cancer. A genotype association study was conducted on 85 chemotherapy-naïve patients with metastatic or inflammatory breast cancer that were evaluated for an extended period after receiving standard-dose chemotherapy followed by high-dose cyclophosphamide, cisplatin, and carmustine. Blood pharmacokinetics were evaluated, and DNA was genotyped for 29 polymorphisms in 17 drug metabolism genes. Patients with cyclophosphamide plasma exposures above the median (implying slower metabolic activation) had a shorter survival than those below the median (1.8 v 3.8 years, respectively; P = .042). Patients having a variant genotype of cytochrome P450 3A4 displayed higher blood concentrations of parent (inactive) cyclophosphamide with the second and third doses (P = .024 and .028, respectively) in addition to slower cyclophosphamide activation over the three doses (P = .031). Median survival for these patients was 1.3 years compared with 2.7 years for those without the variant (P = .043). Similar results were observed for patients carrying a genetic variant of P450 3A5. Median survival for patients with deletions of glutathione-S-transferase M1 gene was 3.5 v 1.5 years for patients with one or both copies (P = .041). Patients with a polymorphism in a gene regulating metallothionein had lower platinum concentrations and shorter survival (P = .033). These data suggest that pretreatment evaluation of drug metabolism genes may explain some interindividual differences in both anticancer drug pharmacokinetics and response. The correlations found here may have implications for other commonly used anticancer drugs.

Circadian Variability of Pharmacokinetics of 5-Fluorouracil and CLOCK T3111C Genetic Polymorphism in Patients With Esophageal Carcinoma

The variations of plasma concentrations of 5-fluorouracil (5-FU) were investigated in 30 esophageal cancer patients treated with repetitive protracted venous infusion (PVI) of 5-FU-based chemoradiotherapy, and in an attempt to find a new possible candidate that explains their variations, CLOCK T3111C genetic polymorphism was examined. The patients have received 2 courses of chemoradiotherapy consisting of 2 cycles of 5-day PVI of 5-FU (400 mg/m/d) with cisplatin and concurrent radiation. The plasma concentrations of 5-FU were determined at 5 PM on day 3 and 5 AM on day 4 after the beginning of each 5-FU infusion. The CLOCK T3111C genotype was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) and by direct sequencing. Plasma concentrations were measured in 239 samples. In the first course, the plasma concentrations of 5-FU at 5 AM were significantly lower than those at 5 PM in the first cycle, whereas a similar tendency was observed in the second cycle, although not significantly (Wilcoxon signed-rank test). The plasma concentrations of 5-FU at 5 PM and 5 AM in the second cycle were both significantly higher than those in the first cycle, and their coefficient of variation in the former was also significantly smaller than that in the latter. These phenomena in the first course were also observed in the second one. These results revealed the elevation of plasma drug concentration and its reduced circadian variation during repetitive PVI of 5-FU. In 5-FU-based chemotherapy, its administration schedule should be made in consideration of these phenomena. The CLOCK T3111C genotype did not have a significant impact on the variation of the plasma concentrations of 5-FU in this study population. Further studies are needed to clarify the mechanism of these phenomena and to identify an easy-to-assess marker of circadian rhythms for use in individualizing delivery of 5-FU.

Tau-assoziierte genetische Polymorphismen bei frontotemporaler Demenz

[corrected] To evaluate tau-associated genetic polymorphisms in patients with sporadic frontotemporal dementia (FTD) and healthy control subjects. Tau-gene sequence of 30 patients with FTD and 30 healthy controls was analysed by polymerase-chain-reaction (PCR). Subsequent sequencing was performed to identify exonic and intronic differences between both groups. The following polypmorphisms, which are localized closely to each exon-intron-border, have been identified: In 37 % (n = 11) of the control subjects three different intronic polymorphisms occur simultaneously (Intron 2, 263, C --> Y; Intron 3, 590, A --> R; Intron 11, 150, G --> A). In the FTD group, this coexistance has been observed only in 17 % (n = 5). In how far there exists a significant correlation between the newly identified triple polymorphism in the Tau gene and an alternated risk for FTD must be evaluated in a lager population. The proximity of these polymorphisms to the exon-intron border would facilitate functional influences on gene expression patterns. These preliminary results described, above potentially point to further pathogenetic factors in the genesis of FTD.

Specific serum IgE levels and FcɛRIβ genetic polymorphism in patients with penicillins allergy

Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcepsilonRIbeta polymorphism. The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE (P=0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)- or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02, and 0.011, respectively). The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.

Influence of coagulation factor 13A (F13A) gene variants on overall survival (OS) of ovarian cancer patients

5002 Background: Abnormalities of haemostasis, including hyper-coagulation and enhanced fibrinolysis, are evident in advanced epithelial ovarian cancer (EOC). Polymorphisms of the F13A gene influence both F13 enzyme activity, and characteristics of the cross-linked product. We therefore evaluated F13A genetic polymorphisms in patients with EOC. Methods: 260 peripheral blood DNAs, from EOC patients, were examined for five F13A polymorphisms: Val34Leu, Tyr204Phe and Pro564Leu by the TaqMan™ assay and Val650Ile and Glu651Gln by PCR-SSCP. Results: Median age was 61 (29–89). With a median follow-up of 38 months (range 265 months), median overall survival (OS) was 99 months. The frequency of each genotype did not differ from those found within the normal healthy population. No association was identified between stage at presentation and any of the five genotypes. Significant associations were identified between overall survival and genotype. 650Ile was associated with shorter OS (p=0.008 by logrank test). Carriage of the 34Leu allele was associated with longer OS in patients with FIGO stage III and IV (p=0.0219 by logrank test). When a multivariate cox regression model comprising stage, the Val650Ile and Val34leu polymorphisms was performed, these polymorphisms independently predicted OS (see table). Conclusion: F13A Val34Leu and Val650Ile genetic polymorphisms may be valuable prognostic factors in ovarian cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Yorkshire Cancer Research; West Riding Medical Research Trust

Influence of coagulation factor 13A (F13A) gene variants on overall survival (OS) of ovarian cancer patients

5002 Background: Abnormalities of haemostasis, including hyper-coagulation and enhanced fibrinolysis, are evident in advanced epithelial ovarian cancer (EOC). Polymorphisms of the F13A gene influence both F13 enzyme activity, and characteristics of the cross-linked product. We therefore evaluated F13A genetic polymorphisms in patients with EOC. Methods: 260 peripheral blood DNAs, from EOC patients, were examined for five F13A polymorphisms: Val34Leu, Tyr204Phe and Pro564Leu by the TaqMan™ assay and Val650Ile and Glu651Gln by PCR-SSCP. Results: Median age was 61 (29–89). With a median follow-up of 38 months (range 265 months), median overall survival (OS) was 99 months. The frequency of each genotype did not differ from those found within the normal healthy population. No association was identified between stage at presentation and any of the five genotypes. Significant associations were identified between overall survival and genotype. 650Ile was associated with shorter OS (p=0.008 by logrank test). Carriage of the 34Leu allele was associated with longer OS in patients with FIGO stage III and IV (p=0.0219 by logrank test). When a multivariate cox regression model comprising stage, the Val650Ile and Val34leu polymorphisms was performed, these polymorphisms independently predicted OS (see table). Conclusion: F13A Val34Leu and Val650Ile genetic polymorphisms may be valuable prognostic factors in ovarian cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Yorkshire Cancer Research; West Riding Medical Research Trust

GSTP1, GSTM1, and GSTT1 genetic polymorphisms in patients with cryptogenic liver cirrhosis.

We investigated glutathione S-transferase (GST) P1 Ile (105) Val, T1, and M1 polymorphisms in 45 patients with documented cryptogenic cirrhosis and 56 healthy control subjects. Polymerase chain reaction-based procedures were performed in the studied populations to confirm the genotypes of GSTT1, M1, and P1. Ile/Val and Val/Val GSTP1 genotypes were more frequent in the patients with cirrhosis (n=39, 87%) than in the control subjects (n=10; 18%) (odds ratio [OR] 34.04; 95% confidence interval [CI] 10.70 to 108.31, P<0.001). Among these patients with cirrhosis, 16 were heterozygous and 23 were homozygous, whereas only one person in the control group was homozygous. The GSTM1 null genotype was also more prevalent in cirrhotic patients than in healthy control subjects (OR 6.83, 95% CI 2.53 to 18.42, P<0.001). The rate of GSTT1 deletion did not show a significant difference between the two groups (OR 2.35, 95% CI 0.76 to 7.28, P=0.111). To our knowledge, this is the first evidence that GSTP1 and GSTM1 polymorphisms may be related to the development of cirrhosis by unknown mechanisms. The significant association of cryptogenic cirrhosis with Val/Val GSTP1 genotype encoding a low detoxification activity protein implicates this polymorphism as a risk factor for the occurrence of the disease.

The amount of calcium-deficient hexagonal hydroxyapatite in aortic valves is influenced by gender and associated with genetic polymorphisms in patients with severe calcific aortic stenosis.

The study evaluated the relationship between cardiovascular risk factors (CRF), gene polymorphism, calcification and fibrosis of stenotic aortic valves. The calcium content of 187 excised stenotic aortic valves was determined using atomic absorption spectroscopy. Hydroxyproline content was quantified. Left-heart catheterization was performed. CRF and genotypes of the interleukin 10, connective tissue growth factor (CTGF) and chemokine receptor 5 (CCR5) polymorphisms were assessed. Calcification consisted of Ca-deficient hexagonal hydroxyapatite, Ca(10 - x)(HPO4)x(PO4)(6 - x)(OH)(2 - x); with 0<or=x<or=1. Calcification (quintiles) was positively associated with the mean gradient across the aortic valve (44 +/- 14, 52 +/- 17, 54 +/- 16, 60 +/- 15, 68 +/- 19 mm Hg; p<0.001). Males (n=101) had a higher degree of calcification (26.1 +/- 8.9 vs 20.8 +/- 9.2 mass%; p<0.001), despite the same mean gradient across the aortic valve (56 +/- 17 vs 56 +/- 19 mm Hg; p=0.958). CRF were not, whereas interleukin 10 polymorphisms -1082, -819, and -592 were significantly associated with the degree of calcification. Furthermore, if certain allele carriers had additionally the rare CCR5 or CTGF allele the degree of calcification was higher. Calcification of stenotic aortic valves consists of Ca-deficient hexagonal hydroxyapatite. Gender and genetic polymorphisms have an impact on the degree of aortic valve calcification.

The role of −850 tumor necrosis factor-α and apolipoprotein E genetic polymorphism in patients with Down's syndrome-related dementia

Down's syndrome (DS) is a disease with a complex etiology. It is likely that other factors besides genes located on chromosome 21 may play a role in clinical features of affected patients. Tumor necrosis factor-α (TNF-α) (6p21.3) and apolipoprotein E (APOE) (19q13.2) are candidate genes as they interact with the brain deposition of Aβ, one of the neuropathological hallmarks in DS. We examined 136 DS patients and 113 controls for −850 TNF-α and APOE polymorphisms. The −850T frequency in DS was significantly higher than in controls (P<0.005, OR 2.05, 95% CI 1.22–3.49) while the APOE E4 allele was negatively selected in patients compared to normal subjects (P<0.005, OR 0.38, 95% CI 0.20–0.71). Our findings suggest that the −850T allele, which is more common among patients at high risk of dementia such as those with DS, might eventually play a role in the development of dementia; no inference on the role of the allele APOE E4 in DS-related dementia may be derived from our results.

The role of −850 tumor necrosis factor-α and apolipoprotein E genetic polymorphism in patients with Down's syndrome-related dementia

Down's syndrome (DS) is a disease with a complex etiology. It is likely that other factors besides genes located on chromosome 21 may play a role in clinical features of affected patients. Tumor necrosis factor-α (TNF-α) (6p21.3) and apolipoprotein E (APOE) (19q13.2) are candidate genes as they interact with the brain deposition of Aβ, one of the neuropathological hallmarks in DS. We examined 136 DS patients and 113 controls for −850 TNF-α and APOE polymorphisms. The −850T frequency in DS was significantly higher than in controls ( P<0.005, OR 2.05, 95% CI 1.22–3.49) while the APOE E4 allele was negatively selected in patients compared to normal subjects ( P<0.005, OR 0.38, 95% CI 0.20–0.71). Our findings suggest that the −850T allele, which is more common among patients at high risk of dementia such as those with DS, might eventually play a role in the development of dementia; no inference on the role of the allele APOE E4 in DS-related dementia may be derived from our results.

»Medizinische Versorgung in der Praxis« - eine Modellstudie zur Verbesserung der hausärztlichen Versorgungsforschung in Deutschland

primary care using computerized patient records. These data are used to assess adherence to evidence-based guidelines (process measures) and clinical results (outcome measures) considering selected diseases as examples (asthma/COPD, heart failure, urinary tract infection). Several other aspects of the mentioned diseases are investigated in patients from the participating practices: • Modification of the responsiveness to topical steroids by genetic polymorphisms in patients with asthma/COPD and their influence on the course of disease. Acceptance of genetic testing in patients with asthma and COPD. • Integration of clinical guidelines for urinary tract infection in German general practices and adjustment to the needs of individual patients. • Problems of care for patients with heart failure at the interface general practice/ hospital and improvement of early diagnosis of the disease.

Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes

Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polymorphisms of the PON1 gene and investigated PON1 enzyme activities as paraoxonase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 concentration in 106 patients with type 2 diabetes and 161 control subjects. All 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no difference in serum PON1 concentration between the patient and control groups. The specific activities of PON, ARYL, and DIAZ in patients were 6.82 ± 3.14 nmol · min−1 · U−1 (mean ± SD, U; unit for serum PON1 concentration), 4.77 ± 0.17 μmol · min−1 · U−1, and 193 ± 92 nmol · min−1 · U−1, respectively, whereas those in controls were 9.33 ± 3.92 nmol · min−1 · U−1, 5.36 ± 0.14 μmol · min−1 · U−1, and 242 ± 103 nmol · min−1 · U−1, respectively. There was no significant difference in the allelic frequencies of −108C/T, 55L/M, or 192Q/R between the patient and control groups. When each enzyme activity was compared between the patient and control groups in each genotype subgroup, all activities were lower in the patient group. The PON and ARYL activities were lower in patients with retinopathy or nephropathy than in those without such complications, and the ARYL activity was also lower in patients with neuropathy. In conclusion, all specific enzyme activities of PON1 were lower in patients with type 2 diabetes independent of the −108C/T, 55L/M, or 192Q/R polymorphism, and this impaired PON1 function may be involved in development of diabetic microangiopathy. Copyright © 2000 by W.B. Saunders Company

Serum paraoxonase enzyme activities and genetic polymorphisms in patients with type 2 diabetes

Serum paraoxonase enzyme activities and genetic polymorphisms in patients with type 2 diabetes

Correlation Between Primary Tuberculous Pleurisy and NRAMP1 Genetic Polymorphism

BACKGROUND: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, we determined the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined. METHODS : 56 Fifty-six primary tuberculous pleurisy patient (,) who were diagnosed by pleural biopsy(,) were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. 3 Three genetic polymorphisms of NRAMP1 (,) such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR)(,) were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used. RESULTS: The frequencies of mutanat mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the both two groups(p=0.079). Odds The odds ratios(,) which are a comparison with wild genotype for determining mutant genotypes(,) were 8.022(95% confidence interval=2.422 ~26.572) for INT4 and 5.733(95% confidence interval=1.137 ~28.916) for 3'UTR which were ;these were statistically significant. But the odds ratio for D543N was not significant. In the combined analysis of the INT4 and 3'UTR polymorphisms, as compared with GG/++ homozygotes, (delete) the odds ratios were 6.000(95% confidence interval=1.461 ~ 24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610 ~121.754) for GC/+del when compared with GG/++ homozygotes which ;these were statisticallysignificant. CONCLUSION: Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.

Insertion/deletion polymorphism of the angiotensin I—converting enzyme gene in patients with hypertension, non—insulin-dependent diabetes mellitus, and coronary heart disease in Taiwan

An insertion/deletion (I/D) polymorphism of the angiotensin I—converting enzyme (ACE) gene has been identified that determines most of the plasma ACE activity genetically. Association of the D allele with insulin sensitivity and of the D/D genotype with coronary heart disease (CHD) has been reported in various ethnic populations. To study the role of this genetic polymorphism in patients with hypertension, non—insulin-dependent diabetes mellitus (NIDDM), and NIDDM with CHD in a Taiwanese population, we used a polymerase chain reaction (PCR)-based genotyping technique with an insertion-specific primer for confirmation of the I allele. One hundred ninety-seven unrelated normal controls, 67 subjects with hypertension, 107 subjects with NIDDM, and 70 subjects with NIDDM and CHD were recruited for this study; all were Han Chinese. Subjects without a history of diabetes were studied by a standard 75-g oral glucose tolerance test. Hypertension was diagnosed according to the Fifth Joint National Committee criteria, and CHD was confirmed by a history of acute myocardial infarction and coronary angiographic intervention. The frequency of the I allele of the ACE gene in the normal population was 64.2%, which was higher than reported in white populations. The prevalence of the I allele of the ACE gene was not significantly increased in subjects with hypertension (73.1%), NIDDM (62.1%), and NIDDM with CHD (65%) compared with healthy controls. The I allele of the ACE gene did not correlate with demographic and metabolic variables. I/D polymorphism of the ACE gene is not a marker for hypertension, NIDDM, or CHD in this Taiwanese population.

Influence of Apolipoprotein(a) Genetic Polymorphism on Serum Lipoprotein(a) Concentration in Patients with Ischemic Cerebrovascular Disease

Increased serum lipoprotein(a) levels are an independent risk factor for ischemic cerebrovascular disease, even in normocholesterolemic and normotri-glyceridemic subjects. The aim of the present study was to investigate apolipo-protein(a) genetic polymorphism in patients with ischemic cerebrovascular disease and to assess its influence on serum lipoprotein(a) levels, since previous data on this topic are lacking. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in 88 men with ischemic cerebrovascular disease (43 atherothrombotic, 25 lacunar, and 20 of unknown type) and in 129 (100 men and 29 premenopausal women) healthy subjects as a control group. Apolipoprotein(a) phenotype frequencies in patients with ischemic cerebrovascular disease did not differ from those of controls. Both patients and controls with phenotype S2 had higher serum lipoprotein(a) levels than those with phenotype S4. It should be emphasized that serum lipoprotein(a) levels were significantly higher in patients with S4 phenotype compared with controls with the same phenotype (12 ± 1.4 and 7 ± 1.4 mg/dl, mean ± SEM, respectively, p < 0.05) as well as for those with S2 phenotype (30 ± 7.9 and 10 ± 2.5 mg/dl, respectively, p < 0.005). Comparison of the apolipoprotein(a) phenotype frequencies showed no significant differences between the 43 patients with atherothrombotic stroke and the 25 with lacunar infarction. However, the Lps1 allele was found more frequently among patients with atherothrombotic stroke, whereas the Lps4 allele was more common among patients with lacunar infarction. Apolipoprotein(a) genetic polymorphism clearly influences serum lipoprotein(a) levels in patients with ischemic cerebrovascular disease, although environmental and/or other genetic factors not related to apolipopro-tein(a) polymorphism must play a role in raised serum lipoprotein(a) levels in these patients.

The distribution of genetic polymorphisms in patients with Down's syndrome.

The distributions of serum complement C3, haptoglobin and transferrin and erythrocyte acid phosphatase, adenylate kinase, 6‐phosphogluconate dehydrogenase and phosphoglucomutase 1 polymorphisms were determined in 171 persons with Down's syndrome and in a control group of 200 normal, healthy persons. In Down's syndrome, unusual phenotypic proportions were observed in the haptoglobin and acid phosphatase systems, while deviations from Hardy‐Weinberg equilibrium were found in the complement C3, acid phosphatase and phosphoglucomutase 1 polymorphisms. The proportion of persons with Down's syndrome of acid phosphatase type A declined linearly with age.