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PubMed2002

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene is not associated with coronary artery disease in a hospital-based Taiwanese population.

We studied whether the 27 base pair (bp) tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene was associated with coronary artery disease (CAD) in a hospital-based Taiwanese population. We included 219 consecutive patients who underwent coronary angiography at our institution. Two alleles, containing 4 (eNOS4a) and 5 repeats (eNOS4b), were identified after polymerase chain reaction amplifying intron 4 of the eNOS gene. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 77.9, 21.5 and 0.6% in CAD subjects, and 80, 20 and 0% in control subjects (Fisher's exact test, p = 0.90), respectively. The odds ratio (OR) for CAD in patients with at least one eNOSa allele was 1.2 (0.5-2.9) after adjustment for classical CAD risk factors. The eNOS4a allele was not associated with the severity of CAD (Fisher's exact test, p = 0.90) and the occurrence of acute myocardial infarction (AMI) or unstable angina (adjusted OR 0.6, 0.3-1.6) in patients with CAD. In conclusion, the 27-bp repeat polymorphism of the eNOS gene was not associated with CAD and the occurrence of AMI or unstable angina in a hospital-based Taiwanese population.

Aged↗

PubMed2004

An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors.

This study tested the hypothesis that the number of CA single sequence repeat (CA-SSR) in the intron 1 of the epidermal growth factor receptor (egfr) gene, which affects transcription efficiency of the gene, is associated with the response to EGFR inhibitors. To this end, we determined the number of CA dinucleotides in the intron 1 of the egfr gene in a panel of 12 head and neck cancer cell lines that lack egfr gene amplification and measured the expression of EGFR (mRNA and protein), as well as response to EGFR inhibition. Cells with lower number of CA dinucleotides in the CA-SSR had higher expression of the EGFR gene and protein and were more sensitive to the inhibitory effects of erlotinib, a small molecule inhibitor of the EGFR tyrosine-kinase. Phenotypic modification by silencing EGFR mRNA expression in a susceptible cell line induced resistance to the drug. The number of CA dinucleotide was equivalent in genomic and tumor DNA obtained from 30 patients with head and neck cancer. In a clinical study in colorectal cancer, subjects with lower number of CA dinucleotide frequently developed skin toxicity, a feature that is related to the antitumor activity of this class of drugs. These results suggest that polymorphic variations in the intron 1 of the egfr gene is associated with response to EGFR inhibitors and may provide an explanation as to why the development of skin toxicity is associated with a favorable outcome in patients treated with these agents.

Cell Line, Tumor↗

PubMed2007

Lack of association between the microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene and bronchiectasis among Koreans.

BACKGROUND AND OBJECTIVE: The genetic factors for the development of bronchiectasis are not well understood in most patients. The aim of this study was to elucidate the possible association between bronchiectasis and guanine-thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2 (TLR2), which has a crucial role in adaptive as well as innate immunity. METHODS: A total of 194 patients with bronchiectasis and the same number of age- and gender-matched healthy blood donors were prospectively enrolled. The numbers of GT repeats were determined by PCR and gene scans. For further analysis, the alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long alleles (L allele). RESULTS: The overall distribution of alleles was not different between patient and control groups (P = 0.71). In addition, the frequencies of genotypes including short alleles were not different between patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and bacterial colonization (P = 0.48) were not associated with any subclass genotype. CONCLUSIONS: Alleles and genotype including the shorter GT repeats in intron 2 of the TLR2, were not associated with the development, extent and bacterial colonization of bronchiectasis in Koreans.

Adult↗

PubMed2000

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease.

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype.

Aged↗

PubMed2006

The lack of association between monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity among men.

Monoamine oxidase (MAO), a mitochondrial flavine containing enzyme, exists in two isoenzymes, MAO-A and MAO-B. Platelets contain MAO-B subtype, proposed to be a biomarker for different personality characteristics and vulnerability for substance abuse. The most common polymorphism of MAO-B gene, a single base change (A or G) occurs in intron 13. It has been proposed to be a functional polymorphism, controlling the activity of MAO-B in platelets. The aim of the study was to determine the association between platelet MAO-B activity and MAO-B intron 13 polymorphism in 225 racially and ethnically uniform healthy Caucasian men of the Croatian origin. Our results showed that platelet MAO-B activity did not differ between subjects subdivided into those with < > or < >. This polymorphism of the MAO-B gene did not control the activity of the MAO-B in platelets. Platelet MAO-B activity was associated only with the smoking status, and it was significantly decreased in smokers when compared to nonsmokers. No significant association was found between MAO-B polymorphism and smoking status. In healthy individuals of the Croatian origin, the studied MAO-B polymorphism showed a lack of functional importance in regulating MAO-B activity in platelets. Since different populations may vary in the association between functional polymorphism and the MAO-B activity, and the genotype of transcription factor AP-2 beta was reported to be associated with altered platelet MAO-B activity, and with specific personality traits, further studies on different populations should be conducted to elucidate the molecular mechanism/s regulating platelet MAO-B activity.

Adult↗

PubMed1993

PCR analysis of DNA from 70-year-old sections of rodless retina demonstrates identity with the mouse rd defect.

Rodless retina (gene symbol, r) was discovered in mice by Keeler 70 years ago and was first described in this journal as an autosomal recessive mutation leading to "the absence of the visual cells (rods), the external nuclear layer, and the external molecular layer" [Keeler, C. E. (1924) Proc. Natl. Acad. Sci. USA 10, 329-333]. The mutation was studied by Keeler and others in the United States and Europe over the next decade, but Keeler's stock was destroyed in 1939, and mice definitively related to his by pedigree and progeny tests also appeared to have been lost by the end of World War II. In the early 1950s Brückner in Basel recognized mice with a similar retinal phenotype. Investigators in London and Strasbourg analyzed descendants of Brückner's mice and concluded, on the basis of different pathogenesis from r, that they carried a new mutation, which came later to be called retinal degeneration, rd. The relationship of r and rd has been unsettled ever since. Now that the rd phenotype is known to be due to a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene, we hoped to settle the question by direct analysis of r DNA. DNA was liberated from 70-year-old histological sections of +/r and r/r eyes, the only extant r DNA, and the regions encompassing the nonsense mutation amplified by the polymerase chain reaction (PCR). Sequence analysis of the PCR products revealed the presence of the same nonsense mutation and two intron polymorphisms in r DNA. PCR and direct sequence analysis of 11 strains of mice known to carry rd (or a similar allele) also revealed the presence of the nonsense mutation and the same intron polymorphisms. The fact that all r and rd mice contain an identical defect and intron polymorphisms in the phosphodiesterase beta-subunit gene settles beyond reasonable doubt that a single mutation arising > 70 years ago is now widely distributed through inbred mouse strains. Because of the extensive use of the name in publications of the past 40 years, we propose that the gene continue to be designated retinal degeneration, rd.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans.

The observation that Toll-like receptor (TLR)2-deficient mice are highly susceptible to mycobacteria suggests that mutations altering TLR2 expression may impair host response to Mycobacterium tuberculosis. We evaluated the association between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were determined by PCR and gene scans for 176 TB patients and 196 controls. The recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including three representative repeats: (GT)13, (GT)20, and (GT)24 were transfected into K562 cells, and luciferase activities were estimated and compared. The expression of TLR2 on CD14+ peripheral blood mononuclear cells (PBMC) from healthy volunteers were measured with flow cytometry. Genotypes with shorter GT repeats were more common among TB patients (49.4 vs 37.7%, P=0.02). This observation was confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats were associated with weaker promoter activities and lower TLR2 expression on CD14+ PBMCs. In conclusion, the development of TB disease in Koreans was associated with shorter GT repeats in intron II of the TLR2 gene. This association is correlated with lower expression of TLR2 through weaker promoter activity for genes with shorter GT repeats.

Adolescent↗

PubMed2000

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease.

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.

Adult↗

PubMed2002

Polymorphism in intron 23 of the endothelial nitric oxide synthase gene (NOS3) is not associated with hypertension.

Nitric oxide (NO) is synthesised in the vascular endothelium by nitric oxide synthase (NOS3) and is an important factor in the regulation of blood pressure. Impaired synthesis of NO due to mutations in the NOS3 gene is associated with hypertension. To date several allelic variants of the NOS3 gene have been identified and their possible linkage with hypertension investigated. We studied the distribution of genotypes and frequency of alleles of the G11T polymorphism in intron 23 of the NOS3 gene in patients with hypertension and in a control group of healthy individuals. The polymorphism was determined by PCR-RFLP analysis. The distribution of genotypes in the patients with hypertension and in the healthy individuals did not differ significantly from the values predicted from Hardy-Weinberg equilibrium for the general population. No major differences in the distribution of the G11T polymorphism in the patients and healthy individuals were found (P > 0.05).

Adult↗

PubMedDate not supplied

An epidermal growth factor receptor intron 1 polymorphism in healthy women in Poland.

The frequency of CA allele combinations was assessed in healthy women from Poland and compared to previously published polymorphism data of individuals from Germany and a Caucasian reference group. There were close similarities between these three geographically and ethnically similar populations. By contrast, the distribution of these alleles in European and Asian (Japan) populations proved to be different. There might therefore be major ethnic differences in allelic frequencies of EGFR intron 1 polymorphism. Our results provide new data on EGFR microsatellite instability and may contribute to the understanding of EGFR gene expression regulation. The clinical relevance of these findings warrants further evaluation.

Adolescent↗

PubMed2000

A novel polymorphism in intron 1a of the human factor VII gene (G73A): study of a healthy Italian population and of 190 young survivors of myocardial infarction.

We have identified a novel polymorphism located in intron 1a of the human factor VII gene, caused by the nucleotide change G to A at position + 73. In a population of 128 healthy individuals from northern Italy, the variant A73 allele had a frequency of 0.21, whereas the frequency of the previously reported 10 bp insertion allele located at -323 in the promoter region was 0.17 and that of the Q353 allele in the catalytic region of the factor VII gene was 0. 20. In 75% of the healthy individuals, the A73 allele was present together with the 10 bp insertion and the Q353 alleles, indicating a strong linkage disequilibrium. The concomitant presence of A73 with both the 10 bp and the Q353 alleles was associated with the lowest factor VII levels, measured as coagulant activity, activated factor VII and factor VII antigen. The G73A polymorphism was also evaluated in 190 survivors of myocardial infarction who had experienced the event before the age of 45 years and in 179 individuals with a negative exercise test matched with patients for sex, age and geographical origin. Patients carrying the A73 allele associated with lower factor VII levels tended to have a lower risk of myocardial infarction (adjusted odds ratio 0.54; 95% confidence intervals 0.29-0.99). In conclusion, we found a novel variant allele in intron 1a of the human factor VII gene that is often associated in healthy individuals with the 10 bp and Q353 alleles in the promoter and catalytic region of the same gene. This intronic mutation, alone or in association with other factor VII gene polymorphisms, might confer protection against myocardial infarction in the young.

Adolescent↗

PubMed1996

Point mutation analysis of the FMR-1 gene in autism.

We have analysed all 17 exons of the human FMR-1 gene for mutations in autistic individuals using single-stranded conformational polymorphism (SSCP) analysis. We have identified three new polymorphisms. SSCP DNA fragment shifts were found for exons, 5, 10 and 11 in autistic individuals and in normal controls. Sequence analysis showed the exon 10 and 11 polymorphisms to result from base substitutions within introns, 14 and 73 bp downstream from the splice site respectively. In exon 5, a G to A base substitution at codon 138 has no effect on amino acid sequence. The intronic polymorphism adjacent to exon 10 was analysed amongst two groups of unrelated autistic individuals-one from the UK and one from Germany- and amongst a control population. Comparison of allele frequencies between Caucasian autism cases and Caucasian controls show a significant increase in the presence of the polymorphic intronic sequence 3' to exon 10 (Fisher's exact test, P = 0.01). The base change is at a position where it is unlikely to affect splicing of the FMR-1 transcript and is most likely a neutral variant that has only a spurious false positive association with autism. However further linkage disequilibrium analyses are justifiable. The positive association with autism should be explored in further samples to determine whether it has any validity as a genetic marker for autism.

Autistic Disorder↗

PubMed2004

Poly (AT) polymorphism in intron 11 of the XPC DNA repair gene enhances the risk of lung cancer.

Reduced DNA repair capacity due to inherited polymorphisms may increase the susceptibility to smoking-related cancers. In this report, we investigate the relationship between xeroderma pigmentosum complementary group C poly (AT) insertion/deletion polymorphism (XPC-PAT) of the XPC gene and lung cancer risk in a hospital-based case-control study of 359 newly diagnosed lung cancer patients and 375 control subjects matched on age, sex, and catchment area. The XPC genotype was determined by PCR-RFLP, and the results were analyzed using logistic regression, adjusting for relevant covariates. We found that the frequency of the PAT+/+ genotype was higher in the cases (20.6%) than in the controls (14.1%; P = 0.057) and that the PAT+/+ subjects were at significantly increased risk for lung cancer [adjusted odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.55]. Stratified analysis revealed that the risk was higher in former smokers (OR, 2.15; 95% CI, 1.07-4.31) and older people (OR, 2.76; 95% CI, 1.02-7.51), although this probably occurs due to 63.4% of cases older than 73 years being ex-smokers. When stratified by histologic type, the variant genotype was associated with statistically significant increased risk for squamous cell carcinoma (OR, 1.93; 95% CI, 1.06-3.51). In conclusion, our findings support the hypothesis that PAT and intron 11 C/A XPC polymorphisms are linked in the Spanish population and may contribute to the risk of developing lung cancer probably due to a higher frequency of deletion of exon 12 and reduced DNA repair capacity of the XPC protein.

Adult↗

PubMed2005

Allelic polymorphism in introns 1 and 2 of the HLA-DQA1 gene.

Human leukocyte antigen (HLA) class II antigens are highly polymorphic membrane glycoproteins, encoded by the A and B genes of DR, DQ, and DP. The polymorphism is mainly located in exon 2, with the exception of DQA1. Of the 27 DQA1 alleles presently known, 18 cannot be identified on the basis of exon 2 alone, but need additional information from the other exons. DQA1 has been reported to be the most ancient class II gene. For evolutionary comparison and to assess the degree of polymorphism outside the exons, the sequences of introns 1 and 2 were determined from 30 different cell lines, encompassing 15 different DQA1 alleles. The sequences revealed major nucleotide differences between the different lineages, whereas within each lineage few differences were present. Phylogenetic analysis of intron and exon sequences confirmed this lineage specificity. Altogether, the present data indicate that the HLA-DQA1 lineages represent ancient entities. The observed variation of the introns in alleles with identical exon sequences implicates conservative selection of the exons within a given lineage. Intron sequences may provide the means to set up an accurate typing system.

Base Sequence↗

PubMed2004

[Polymorphism in intron 2 of crucian carp GH I gene].

High length and nucleotide polymorphisms in intron2 of GH I gene were detected in 162 individuals,which were from seven wild crucian carp colonies, two goldfish colonies and one Fangzheng crucian carp colony. Using denaturating polyareylamide gel electrophoresis (DPAGE) and single-strand conformation polymorphism (SSCP), seven length variants and 15 haplotypes were identified in these fishes. The length types and haplotypes diversity was 4.32% and 9.26%, respectively. Sequence analysis of the 15 haplotypes indicated the following results: (1) The size of intron2 varied from 243 to 263 bp. In the 15 haplotypes,the average percentages of the four bases (A,T,G and C) were 34.13%, 37.36%, 15.13% and 13.38%, respectively; the frequency of G + C(28.51%) was much lower than that of A + T (71.49%). The GT/AG domain was found in exon-intron junctions,which was the 5' and 3' splice donor and acceptor sites in higher eukaryotic gene introns. The similarity sequence of GTAAGTA was located on the junction between exon2 and intron2. And there existed a richer pyrimidine region (TTTGCCTTTTGTTATC) near the 3' end of intron2. (2) The seven length variants (A, B, C, D, E, F and G) were determined to be 189, 196, 204, 205, 206, 207 and 209 bp, respectively. The polymorphism resulted from the variable repeat number of T (N = 0, 8, 9, 10, 11 and 13) and the difference in one or two motifs deletions of TGAAAAC, TT and GAGTG. (3) Compared the sequences of the 15 haplotypes, 17 substitution sites were observed, of which two were of transversion sites and 15 were of transition sites. Obviously, the transition mutations (88.24%) were more frequent than transversion mutations (11.76%). Analysis of the distributions of the length types, haplotypes and composite genotypes suggested that genetic diversity was varied in different colonies. In the goldfish colonies, only one length type (A), two haplotypes (A1 and A2) and one composite genotype (A1A2) were observed. Two length types (C and D), four haplotypes (C1, C2, D2 and D5) and one composite genotype (C1C2D2D5) presented in the Fangzheng crucian carp colonies. The highest level of genetic diversity was exhibited in the seven wild crucian carp colonies: seven length types (A, B, C, D, E, F and G), 14 haplotypes (A1, A2, A3, B, C1, C2, D1, D2, D3, D4, E1, E2, F and G) and 14 composite genotypes (A1A2A3, A1A2A3B, A1C1C2D1D2D3, A1C1C2D2, A1C1C2D2D3, A1C1C2D3E2, BC1C2D2, BC1C2D3D4, C1C2D2, C1C2D2D3, C1C2D3D4, C1C2D3D4F, C1C2D4, D2E1G) were shared by the seven wild colonies. The numbers of observed length types, haplotypes and genotypes within the wild colonies ranged from 3 to 6, 6 to 10 and 2 to 6, respectively. Whether the length and nucleotide polymorphisms in the intron2 of crucian carp GH I gene were associated with gene expression and gene regulation remained unsolved and required further investigations.

Animals↗

PubMed1995

A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility.

We present a novel polymorphic 8-bp sequence in intron 6 of the p53 gene that maps between bp 55 and 62 of the 3' end of exon 6. Of normal blood samples, 32% were heterozygotic for this polymorphism and display a NN' genotype, whereas 68% of the population is homozygotic for the N genotype. The rare homozygotic genotype N' was detected only in four blood samples of cancer patients. Peripheral blood of gastrointestinal (GI) and breast tumor patients demonstrated a higher incidence of heterozygosity (50%) than that of normal individuals. Analysis of the distribution of this polymorphism in tumor samples showed loss of heterozygosity (LOH). This LOH during tumor progression could exhibit preference to each one of the polymorphic alleles. The rare presentation of one allele and the increased incidence of heterozygosity in carcinoma patients may suggest an association between this polymorphism with cancer predisposition and susceptibility. The fact that genetic alterations occurring in noncoding regions may play a role in tumor development only further increases the extent of involvement of p53 in carcinogenesis.

Base Sequence↗

PubMed1999

Analysis of human leukocyte antigen-G polymorphism including intron 4 in Japanese couples with habitual abortion.

PROBLEM: The purpose of this study was to clarify whether there is a difference between the allele frequency of human leukocyte antigen (HLA)-G in healthy Japanese people and that of Japanese couples with habitual abortion. METHOD OF STUDY: Exons 2, 3, 4, and intron 4 of the HLA-G gene were analyzed in 20 couples with habitual abortion, using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Intron 4 of the HLA-G gene was also analyzed in 54 healthy individuals. The nucleotide sequence of the PCR product of intron 4 was further determined by direct sequencing. RESULTS: Two kinds of nucleotide sequence were identified in intron 4 of the HLA-G gene, one of which was identical to that of HLA-G*01011, and the other was identical to that of HLA-G*01012, G*01013, and G*0104. The frequency of each allele in affected women and their husbands did not significantly differ from that of healthy individuals, and no mutation was found in any affected couple. CONCLUSION: HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of habitual abortion.

Abortion, Habitual↗

PubMedDate not supplied

Genetic analysis of H-ras intron-1 polymorphic and variable tandem repeat regions in human breast cancer.

H-ras is a member of the ras superfamily of genes. This gene encodes for a 21 kDa protein (p21) which is located on the inner surface of the plasma membrane. Ras genes are involved in a wide variety of human tumors, and there is a known correlation between H-ras activation and breast carcinogenesis. H-ras contains a polymorphic region, a repeated hexanucleotide -GGGCCT - located in intron 1 close to the 5' of the gene (HRM region). Three alleles of this region, P1, P2 and P3, have been identified that contain two, three and four repeats of the hexanucleotide, respectively. H-ras possesses a minisatellite DNA of the variable tandem repeat (VTR) which is located 1000 bp downstream of the gene displaying linkage disequilibrium with HRM. The purpose of this study was to estimate the frequency of P1, P2 and P3 in the normal population and in patients with breast cancer. We studied 56 biopsy specimens from patients with breast cancer, 61 normal blood samples, and 30 pairs of normal and tumoral breast tissues for VTR analysis. There was a difference in the distribution of P1, P2 and P3 alleles between normal and breast cancer samples. The frequency of P1 homozygosity was shown to be almost twice as high in women with breast cancer compared to healthy women (72% versus 39%). These results suggest that P1 homozygosity may be considered as a potential risk factor in breast carcinogenesis. In VTR analysis one sample presented a shift in mobility, but no polymorphism in the BstN I pattern of the 28 bp repetition core was observed.

Aged↗