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PubMed2005

[Association analysis on the polymorphisms of PCOL2 and Sp1 binding sites of COL1A1 gene and the congenital dislocation of the hip in Chinese population].

OBJECTIVE: To investigate the polymorphism distribution of the PCOL2 and Sp1 binding sites of the collagen type I alpha 1(COL1A1) gene in Chinese population and explore their relationship with congenital dislocation of the hip (CDH). METHODS: The PCOL2 polymorphism (-1997 G/T) in COL1A1 promoter and the Sp1 polymorphism (1546 G/T) in intron 1 were genotyped in 243 members from 81 CDH nuclear family trios by the technique of polymerase chain reaction-restriction fragment length polymorphism, and then transmission disequilibrium test was used to analyze the data of genotypes. RESULTS: No statistically significant association was observed between CDH and PCOL2 polymorphism. Significant differences of genotype and allele frequency distributions were detected between the Chinese population and the Caucasian population in Spain, and between the Chinese population and the Caucasian population in America. The allele at the Sp1 site that has been found to be polymorphic in other populations was not found in Chinese. CONCLUSION: There exists racial difference in the distribution of the PCOL2 and Sp1 polymorphisms of COL1A1 gene. The results suggest that the PCOL2 and Sp1 polymorphisms may not be the major susceptibility gene of CDH in Chinese population.

Asian People↗

PubMed2005

[Association between CCR5 promoter polymorphisms and hepatitis B virus infection].

BACKGROUND/AIMS: Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. CCR5 promoter polymorphisms are known to be associated with HIV infection. However, there has been no report on the association between CCR5 promoter polymorphism and HBV infection. Therefore, we investigated the relationship between the CCR5 promoter polymorphism and HBV infection. METHODS: A total of 377 patients were classified into two groups according to their HBV infection status: (1) the spontaneous clearance group (SC); HBsAg (-), anti-HBc (+), anti-HBs (+) (2) the chronic HBsAg (+) carrier group (CC); HBsAg (+), anti-HBc (+), anti-HBs (-). CCR5 polymorphisms were detected by employing matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)- based SNP scoring assay, termed Restriction Fragment Mass Polymorphism (RFMP), which exploits the differences in molecular masses between the common allele and rare allele bases of interest. RESULTS: We found that the genotype frequencies of CCR5 A59029G significantly differed between the SC group (n=138) and CC group (n=239) (P<0.05). The CCR5 59029A allelic genotype was associated with an increased risks of chronic infection rather than spontaneous clearance (P=0.002), and the presence of the CCR5 59029G allele was significantly associated with the spontaneous clearance of HBV (P=0.001). Strong linkage disequilibrium between the CCR5-59029 and the CCR5-59353 polymorphic variants was identified. None of the 377 subjects had the CCR5-32 bp deletion mutation. CONCLUSIONS: The CCR5 promoter polymorphisms at position 59029 might play a role in the clearance of HBV infection. This primary experimental evidence needs further studies to clarify the clinical usefulness of CCR5 promoter polymorphisms as a target for the screening or treatment of HBV infection.

Adult↗

PubMed2005

[Polymorphisms screening of PON gene cluster].

To identify all putative functional polymorphisms of PON gene cluster in Chinese Han population. Common polymorphisms of PON1, PON2 and PON3 gene were identified by directly sequencing of genomic DNAs derived from 48 randomly selected patients with coronary heart disease. We designed PCR arrays to amplify regions up to about 1kb upstream from transcription-initiation sites, i.e., putative promoter regions, all exons and adjacent non-coding regions. In a total length of 13.9 kb explored, we identified thirty-one SNPs, of which, 17 were first reported. A new coding polymorphism was detected in PON1 gene, which gives rise to amino acid substitutions of arginine (R) for glycine (G) at codon 160, whereas L54M polymorphism, which is common in white population, was not detected in our Han population. Among the five polymorphisms identified in PON3 gene, one in the promoter regions at position -133 (C/A) was located in a potential binding site for transcription factor LF-A1. Allele frequencies of some polymorphisms are significantly different from those reported in Caucasian populations. Complete or nearly complete association between polymorphisms was frequently observed. The identified multiple putative functional polymorphisms in PON gene cluster and their linkage disequilibrium patterns in combination with the population specific frequencies are of values for futher association studies of PON gene cluster with cardiovascular disease.

Aryldialkylphosphatase↗

PubMed2003

ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.

Excision repair cross-complementation group 1 (ERCC1) is a highly conserved protein and an essential member of the nucleotide excision repair pathway. DNA repair is an important mechanism for resistance to platinum-based chemotherapy. Previous studies have shown that ERCC1 gene expression is associated with clinical outcome to platinum chemotherapy in a variety of cancers. Recently, 2 common polymorphisms in the ERCC1 gene have been described. The first is a single nucleotide polymorphism at codon 188 of the ERCC1 gene that causes a C-->T change but codes for the same amino acid, asparagine. This polymorphism may be associated with differential ERCC1 gene expression. The second is also a signal nucleotide polymorphism in the 3'-untranslated region and may affect MRNA stability. We hypothesized that these 2 polymorphisms may be associated with clinical outcome to platinum-based chemotherapy. We assessed the relationship between these ERCC1 gene polymorphism and clinical outcome to platinum-based chemotherapy in 106 patients with advanced refractory colorectal cancer. We found a significant associated between the ERCC1 codon 118 polymorphism and clinical outcome. Patients with the C/C genotype had a median survival of 15.3 months (95% CI, 6.0-12.1) and 11.1 months (95% CI, 5.8-16.2) for those with C/T and T/T genotypes, respectively. The ERCC1 codon 118 polymorphism may be a useful predictor of clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.

Adult↗

PubMed2006

[Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase, methionine synthase and the risk of pancreatic cancer].

OBJECTIVE: To determine whether genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer. METHODS: A hospital-based, case-control study consisting of 101 incident pancreatic cancer cases and 337 controls matched on age, sex and race was conducted to investigate the association between polymorphism in MTHFR and MS, and susceptibility to pancreatic cancer. Genotypes of MTHFR C677T, A1298C and MS A2756G were analyzed by polymerase chain reasction-restriction fragment length polymorphism methods. RESULTS: It was found that multivariate-adjusted odds ratio (ORs; 95% confidence interval) for MTHFR-677CT and 677TT compared with 677CC were 2.17 (1.26 - 3.85) and 3.53 (1.85 - 6.84) respectively, which was in a manner of allele-dose relationship. However, no significant association between the A1298C genotype alone and the risk of cancer was observed which seemed that this polymorphism had a combined effect with the C677T polymorphism. A significant gene-environment interaction was observed between C677T polymorphism and cigarette smoking or alcohol intake. Subjects with variant genotypes who smoked > 17 pack-years had highest risk for developing the cancer, with the OR of 5.58 (2.53 - 12.30). Similarly, the OR (3.27, 1.51 - 7.23) for subjects with variant genotypes of alcohol drinker was significantly higher than that for subjects either having the variant genotype or being drinkers. No association was found between MS A2756G polymorphism and risk of pancreatic cancer in the study. CONCLUSION: These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2006

The polymorphisms of the CYP17 and CYP19 genes in endometrial cancer patients.

Endogenous estrogen exposure is an important determinant of endometrial cancer risk. The CYP 17 and CYP 19 genes encode 17alphahydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. The genes CYP17 and CYP19 are polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the C/T polymorphism in promoter region of CYP17 and G/A polymorphism at position Val80 in CYP19 in subjects with endometrial cancer were investigated. Paraffin embedded tumor tissues were obtained from 100 women with endometrial cancer. DNA from normal endometrial tissue (n=106) served as control. The polymorphisms were determined by PCR-RFLP. The distribution of the genotypes of the C/T polymorphism of CYP17 and G/A polymorphism of CYP19 in both control and patients did not differ significantly (p>0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p>0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the C/T polymorphism of CYP17 gene as well as G/A polymorphism of CYP19 may not be linked with appearance and development of endometrial cancer.

Adenocarcinoma↗

PubMed1991

Genotype establishments for protein C deficiency by use of a DNA polymorphism in the gene.

During the course of structural gene analyses for protein C deficiency, we have confirmed that a T or G nucleotide variation is present at exon 6 of the protein C gene. This single-base substitution was located at the third nucleotide coding for Ser (TCT) at 99 residue, and neither produces an amino acid substitution nor creates a new restriction enzyme site. By using mutagenic primers that could introduce A instead of G at the third nucleotide 3' to the de novo polymorphic site, we have created the polymorphic Xba I site (T/CTAGA) in a more-frequent allele. Polymerase chain reaction using these mutagenic primers and subsequent Xba I digestion of 20 normal Japanese genomic samples showed that the frequency of this new sequence polymorphism designated as PC-493 was 0.18 and that the estimated heterozygosity rate was 28.9%. In Caucasians, the frequency of this polymorphism was 0.25, and a significant difference did not exist between Japanese and Caucasian populations. The examination of the haplotype inter-relationships with PC-493 and the Msp I polymorphism 5' to the protein C gene established that PC-493 gave a 16.7% chance of new information per individual for people who were previously homozygous for the Msp I polymorphism. We have performed a family study of the protein C-deficient pedigree using this sequence polymorphism, and found that the PC-493 DNA polymorphism was a useful marker for tracing the affected gene in protein C-deficient family members.

Base Sequence↗

PubMed2006

[Single nucleotide polymorphisms of three candidate genes in essential hypertension].

OBJECTIVE: To explore the association of single nucleotide polymorphisms (SNPs) of three candidate genes, including T869C of transforming growth factor beta1 (TGF-beta1), -344T/C of aldosterone synthase (CYP11B2) and Gly460Trp of alpha-Adducin with essential hypertension in Chinese Han population. METHODS: Three hundred ninety six hypertensive patients and 214 normotensive subjects were genotyped for T869C, -344T/C and Gly460Trp polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mutagenically separated PCR (MS-PCR), respectively. RESULTS: In single-gene analysis, no association was observed between either CYP11B2 -344T/C or alpha-Adducin Gly460Trp polymorphism and essential hypertension. For female, there were significant difference in genotype distribution and allele frequency of T869C polymorphism (P < 0.02), as compared with subjects with T allele. CC homozygosity had a higher relative risk of hypertension (OR = 2.97, 95% CI, 1.38 to 6.32, P = 0.004), whereas we failed to detect any association between T869C polymorphism and essential hypertension in male. In multiple-gene analysis, the incidence of hypertension was higher in CYP11B2 TT homozygosity than in other CYP11B2 genotypes (OR = 1.99, 95% CI, 1.01 to 3.74, P = 0.03) in the presence of TGF-beta1 CC genotype. CONCLUSIONS: Our results indicated that T869C polymorphism of TGF-beta1 gene might be associated with essential hypertension in female, furthermore, the TGF-beta1 T869C and CYP11B2-344T/C polymorphisms appeared to interact in hypertensive population.

Alleles↗

PubMedDate not supplied

[RET and GFRA1 germline polymorphisms in medullary thyroid cancer patients].

The role of RET and GFRA1 germline polymorphisms in predisposition to sporadic medullary thyroid cancer (MTC) and polymorphisms' modulation effect on clinical features of inherited and sporadic MTC were investigated. Blood samples from 67 MTC patients (22 hereditary and 45 sporadic), 3 asymptomatic mutant RET gene carriers and 178 ethnically matched healthy control individuals were tested. Screening of RET exons and portion of introns 1, 8, 10, 13, 14, 15, 16 and GFRA1 5'-UTR was performed by means of direct sequencing and PCR-RFLP. 8 polymorphic variants of RET gene (exons 11, 13, 14, 15 and introns 1, 8, 13, 14) and 4 GFRA1 polymorphisms in GFRA1 were detected. Linkage disequilibrium was found between RET variants G691S and S904S, L769L and IVS8, S836S and IVS13. In sporadic MTCs, allelic frequency of only one polymorphic RET variant, L769L, was significantly decreased versus control group. In hereditary MTCs, a significant over-representation of S836S and under-representation of S904S sequence variants were observed as compared to sporadic MTCs and controls. No co-segregation was found between individual polymorphisms and phenotype of sporadic MTC. In patients with inherited MTC whose genotype was presented with polymorphic L769L and wild-type S836S, disease onset occurred 20 years later than in individuals with polymorphic L769L and S836S or wild-type L769L (p = 0.01) suggestive of a possible protective role of L769L in MTC development and modulating effect of a combination of L769L with wild-type S836S on clinical outcome of inherited MTC.

Adolescent↗

PubMed2006

[Association between polymorphisms of CYP17 and CYP3A4 genes and intrahepatic cholestasis of pregnancy in Chengdu].

OBJECTIVE: investigate whether polymorphisms in estrogen-metabolizing genes, CYP17 and CYP3A4, are associated with intrahepatic cholestasis of pregnancy (ICP) in Chengdu China. METHODS: The -1931T/C polymorphism in the 5'-untranslated region of CYP17 gene and the -290A/G polymorphism in the 5'-regulatory region of CYP3A4 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 pregnant women with ICP (ICP group) and 100 normal pregnant women (control group) in Chengdu. RESULTS: The T/C polymorphism of the CYP17 gene was shown clearly in ICP and control groups, but the genotype distributions (TT, TC and CC) and allele frequencies (T and C) of CYP17 polymorphism were of no significant difference between the two groups (P > 0.05). No CYP3A4-V (CTP3A4 * 1B) allele was found in the 200 individuals studied. The genotype of CYP3A4 was wt/wt in all the pregnant women. CONCLUSION: The T/C polymorphism of CYP17 gene is not associated with the risk of ICP in Chengdu. There are not -290A/G polymorphism of CYP3A4 gene among pregnunt women in Chengdu.

China↗

PubMedDate not supplied

[Transferase S-glutathione class pi gene (GSTP1) polymorphism in thyroid cancer patients].

INTRODUCTION: One of the potential genes which can increase the risk of cancer is GSTP1 gene. It encodes enzyme called glutathione S-transferase pi class, which is involved in the detoxification of a variety of potential carcinogenic compounds. Polymorphism in this gene can cause the amino acid substitution. This substitution, close to the substrate binding site, changes the enzymatic activity for particular substrates and subsequently increases the risk of carcinogenesis. The aim of this study was to evaluate the function of GSTP1 polymorphism in thyroid cancer and possible association between GSTP1 polymorphism and age at diagnosis. MATERIAL AND METHODS: 103 patients with differentiated thyroid cancer (DTC) and 53 individuals from control group were examined using PCR-RFLP. RESULTS: Statistically insignificant association of studied polymorphisms with thyroid cancer was observed. Comparison of allele frequency between cases and control groups revealed the presence of risk alleles. For the first polymorphism Ile OR = 1.257; 95% CI [0.792-1.997] (p = 0.332), and for the second one Val OR = 1.283; 95% CI [0.6260-2.631] (p = 0.495). The presence of Val/Val (c.313A>G) led to a significant earlier age of onset as compared with other genotypes (p < 0.05). Mean age at diagnosis for Val/Val genotype was 41.1 +/- 15.2, and for Ile/Val + Ile/Ile reached 48.9 +/- 13.2. There was no association between age and genotype for c.341C>T polymorphism. CONCLUSIONS: Statistically insignificant association of GSTP1 gene polymorphism with thyroid cancer was observed in studied group of patients. The Val/Val genotype for c.313A>G polymorphism led to earlier age of tumour diagnosis as compared with other genotypes.

Adolescent↗

PubMed1990

Polymorphism in human T cell receptor alpha chain variable region genes.

Polymorphism of human T cell antigen receptor (TCR)alpha genes was detected by restriction fragment length polymorphism (RFLP). Individual TCR alpha gene segments showed limited polymorphism in that few restriction enzymes revealed polymorphism in genomic DNA samples and when RFLP were detected only two or three allelic forms were observed. A rabbit TCR alpha cDNA clone (VJR5) detected polymorphism in human DNA samples digested with PvuII or MspI. In order to characterize the human V alpha genes detected by the rabbit probe, genomic clones hybridizing with the VJR5 probe were isolated and characterized. A probe derived from a human genomic clone (HUTAVR5) hybridized with some but not all fragments detected by the rabbit VJR5 probe. The data suggest that the rabbit probe hybridized with two distinct human TCR alpha V genes and that polymorphism of each gene was detectable by only one restriction enzyme. In contrast to the limited polymorphism of TCR alpha genes detected by individual markers, extensive heterogeneity of TCR alpha genes was observed in the combination of markers present in haplotypes. Six RFLP were used as TCR alpha markers to define haplotypes in 20 parents and 53 offspring from 10 families and 17 different combinations of markers were observed. The observation that TCR alpha haplotypes include numerous combinations of markers that individually show limited polymorphism suggests that recombination may occur frequently within the TCR alpha gene complex.

Animals↗

PubMed1983

Human lymphocyte polymorphisms detected by quantitative two-dimensional electrophoresis.

A survey of 186 soluble lymphocyte proteins for genetic polymorphism was carried out utilizing two-dimensional electrophoresis of 14C-labeled phytohemagglutinin (PHA)-stimulated human lymphocyte proteins. Nineteen of these proteins exhibited positional variation consistent with independent genetic polymorphism in a primary sample of 28 individuals. Each of these polymorphisms was characterized by quantitative gene-dosage dependence insofar as the heterozygous phenotype expressed approximately 50% of each allelic gene product as was seen in homozygotes. Patterns observed were also identical in monozygotic twins, replicate samples, and replicate gels. The three expected phenotypes (two homozygotes and a heterozygote) were observed in each of 10 of these polymorphisms while the remaining nine had one of the homozygous classes absent. The presence of the three phenotypes, the demonstration of gene-dosage dependence, and our own and previous pedigree analysis of certain of these polymorphisms supports the genetic basis of these variants. Based on this data, the frequency of polymorphic loci for man is: P = 19/186 = .102, and the average heterozygosity is .024. This estimate is approximately 1/3 to 1/2 the rate of polymorphism previously estimated for man in other studies using one-dimensional electrophoresis of isozyme loci. The newly described polymorphisms and others which should be detectable in larger protein surveys with two-dimensional electrophoresis hold promise as genetic markers of the human genome for use in gene mapping and pedigree analyses.

Autoradiography↗

PubMed1997

Corticotropin releasing hormone promoter region polymorphisms in rheumatoid arthritis.

The regulation of the human corticotropin releasing hormone (CRH) gene is of interest since it mediates the interaction of stress events and inflammatory signals on the hypothalamo-pituitary-adrenal axis. Patients with rheumatoid arthritis (RA) have impaired CRH response to stress so that polymorphisms in the 5' regulatory region of the CRH gene could be responsible for decreased CRH responsiveness. To examine whether patients with RA have polymorphisms of the regulatory region of CRH, we amplified fragments of the 3.7 kb genomic DNA from 5 unrelated patients with RA and 2 controls. DNA sequencing revealed 3 nucleotide variants. These variants have been characterized as a T-->C base substitution located at position 1273 (alleles A1 and A2) and at position 2942 (alleles B1 and B2), and a C-->G base substitution located at position 95 (alleles C1 and C2), respectively, of the Genbank entry x67661. These substitutions lead to the destruction of the recognition site for AflIII (position 1273) and CviJI (position 95), and an introduction of a recognition site for BsmAI (position 2942) restriction enzymes, respectively. Three of 5 patients with RA were heterozygous for all 3 polymorphisms observed, while the 2 polymorphisms at positions 1273 and 2942 were represented in one control only. Post polymerase chain reaction (PCR) restriction fragment length polymorphism was performed to investigate the frequency of the polymorphisms in 99 healthy unrelated Caucasians and 28 members of CEPH (Centre d'Etudes du Polymorphisme Humaine) families. The AflIII, BsmAI, and CviJI polymorphisms cosegregate absolutely in both the controls and the CEPH families. The frequency for allele 1 was 0.869, while that for allele 2 was 0.131, with the following observed genotype frequencies: A1/A1 0.75; A1/A2 0.23; A2/A2 0.02. The T-->C base substitution at position 2942 leads to destruction of a consensus sequence for transcription factor GH-CSE2. These novel polymorphisms should therefore be considered in studies of CRH gene expression and may play a role in the pathogenesis of RA.

Animals↗

PubMed1995

A novel clonality assay based on transcriptional polymorphism of X chromosome gene p55.

The clonal nature of cell populations in malignant and myeloproliferative disorders can be determined in female subjects by random-inactivation assays of the X chromosome. Assays utilizing either expression of the G6PD isozymes or DNA-methylation differences between the active and inactive X chromosomes have significant short-comings. We developed a test based on nucleotide #1311 exonic polymorphism of G6PD that allows detection of clonality by determining the transcriptional polymorphism of the active X chromosome using a reverse transcription-polymerase chain reaction-ligase detection reaction (rtPCR-LDR). Since only 18% of females in the United States are informative (heterozygous) for this chromosome with this assay, we searched for other exonic X chromosome polymorphisms. Concentrating on a discrepancy (G or T at cDNA #358) of published sequences of ubiquitously expressed gene, palmitoylated membrane protein for p55, we confirmed this conservative polymorphism at the cDNA level. To detect the genotype of this polymorphism, we established the intron/exon boundary of the first 5' exons and determined the whole sequence of the second intron. We found that the polymorphic site is at the third exon, nine nucleotides downstream from the 294-bp second intron. This close proximity to the intron necessitated the development of a separate PCR-LDR reaction with oligonucleotides for cDNA and genomic DNA. Furthermore, we determined that the p55 gene is subject to X chromosome inactivation. Based on these observations, we developed a novel p55 clonality assay that is reproducible, quantitative, and very sensitive. Screening of 37 randomly selected healthy females of Caucasian, African-American, and Asian origin revealed that 38% of females are informative when this assay is used. We demonstrate a multiple crossover between the G6PD and the p55 polymorphisms (separated by approximately 200 kb), suggesting that these two polymorphisms are in linkage disequilibrium; thus, approximately 50% of female subjects are informative for clonality studies using the two assays.

Base Sequence↗

PubMed1985

Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.

Monoclonal antibodies have been used to demonstrate a polymorphism of human plasma coagulation factor IX antigen in double antibody solid-phase immunoradiometric assays. This polymorphism is detected in an assay where a monoclonal antibody (A-1) adsorbed to microtiter wells is used to bind factor IX from diluted plasma samples. Plasma samples with the factor IX polymorphism have less than 0.2 U/ml of apparent antigen when tested with the A-1 antibody, while assays with other monoclonal antibodies and assays with goat antisera to factor IX show normal amounts of factor IX antigen. Factor IX coagulant activity was normal in samples from donors with the polymorphism. The thin-layer polyacrylamide gel isoelectric focusing pattern of factor IX purified from a donor with the factor IX polymorphism (IXp) was identical to that obtained with factor IX prepared from a donor who did not have the polymorphism (IXn). Purified radiolabeled factor IX prepared from a donor with the polymorphism showed a Ka for the A-1 antibody that was threefold less than that measured for IXn. The gene frequency of IXp in male blood donors is 0.25. This polymorphism may be useful as a marker for the X chromosome in genetic studies on plasma samples. Further studies are necessary to determine the explanation for decreased reaction of IXp with the A-1 monoclonal antibody.

Antibodies, Monoclonal↗

PubMed1985

Analysis of three restriction fragment length polymorphisms in the human type II procollagen gene.

Cloned genomic DNA sequences corresponding to various regions of the human type II procollagen gene were used to analyze the DNA from 78 normal volunteers. Southern hybridization experiments detected polymorphic HindIII, BamHI, and EcoRI sites. The presence of the polymorphic HindIII site results in a 7.0-kilobase (kb) band, and the absence of this site results in a 14.0-kb band. When present, the BamH1 polymorphic site yields a 4.8-kb band, and when absent, yields a 7.2-kb band. The presence of the EcoRI polymorphic site results in a 3.7-kb band, and its absence results in a 7.0-kb band. Each polymorphic site was mapped. Analyses of the data demonstrated that the sites are present in overall gene frequencies of .39 for HindIII, .04 for BamHI, and .02 for EcoRI. Gene frequencies of the polymorphic sites were also studied with respect to race. The polymorphic sites are present in a Hardy-Weinberg distribution in the study population. Study of an extended family demonstrated that the segregation of the HindIII polymorphic site is consistent with Mendelian inheritance.

Deoxyribonuclease BamHI↗

PubMed1998

Angiotensin converting enzyme insertion/deletion polymorphism in French Canadian subjects with premature coronary artery disease.

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been postulated to be associated with CAD in some populations of European descent. As part of a study investigating metabolic and genetic factors in subjects with premature coronary artery disease (CAD), we examined the I/D polymorphism of the ACE gene in 134 subjects with premature CAD (105 men and 29 women, mean age 49 +/- 6 years) and 116 control subjects selected for health (71 men, 45 women; mean age 39 +/- 7 years). Both patients and controls were of French Canadian descent. As expected, significant differences were found between cases and controls with respect to age, plasma lipoprotein cholesterol, presence of smoking, diabetes and high blood pressure after correction for age. Multivariate analysis confirms the importance of age, HDL-C levels, smoking and apo B levels as determinants of CAD. Allele frequencies of the I and D polymorphism were 43.1% and 57.9% in controls, and 48.5% and 51.5% in CAD cases (chi 2 = 0.622, p = 0.430). No significant association between the I/D polymorphism and conventional cardiovascular risk factors, including plasma levels of lipids, lipoprotein cholesterol, diabetes or smoking, was found in cases or controls. Furthermore, the presence of the I/D polymorphism did not correlate with a history of hypertension or a family history of premature CAD in CAD patients. We conclude that, in our selected population, the I/D polymorphism of the ACE gene is not associated with CAD, conventional risk factors, or a family history of CAD. Although our sample size does not allow sufficient power to ascertain that the ACE I/D polymorphism is not associated with CAD, we do not recommend the routine measurement of the ACE polymorphism in our population to determine cardiovascular risk.

Adult↗