SEARCH · PubMed Health

Results for “intronic polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

PubMed2000

[Study on the FcepsilonRI-beta polymorphism and susceptibility of asthma in a Chinese population].

OBJECTIVE: To investigate the linkage between the polymorphisms of FcepsilonRI-beta gene and susceptibility of asthma in a Chinese population. METHODS: Thirty-two families with 192 samples and 122 cases of childhood asthma were studied. A coding variant of E237G was detected by PCR/XmnI restriction endonuclease digestion. Two RsaI polymorphic sites within non-coding region were tested by PCR/RsaI restriction endonuclease digestion. RESULTS: The allele frequencies for all three polymorphisms of FcepsilonRI-beta gene in the Chinese population were markedly different from those published results of Caucasians and Japanese. Comparing asthma family samples with normal control, we found that genotypes containing A allele within intron 2 polymorphic site were associated with asthma (P < 0.05, OR = 2.039). The level of total serum IgE showed significant difference among three genotypes of intron 2 polymorphic site (P < 0.05). The association between A allele and elevated total serum IgE was also significant (P < 0.05, RR = 1.361). We could not find any significant results from the other two polymorphisms, even in the coding variant E237G. CONCLUSION: We were unable to confirm that the FcepsilonRI-beta gene was crucial to the susceptibility of asthma and atopy and did not contribute substantially to variation in IgE levels from both sample groups.

Adolescent↗

PubMed2002

[A study of insertion/delation polymorphism of the angiotensin-converting enzyme gene in pilots].

In order to understand insertion/delation (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in pilots,and to explore the relationship between ACE gene I/D polymorphism and the performance of the pilots, the polymerase chain reaction (PCR) was used to determine the genotypes for an I/D polymorphism in intron 16 of the ACE gene in 118 pilots and 96 healthy subjects as controls. The result showed that the I/D polymorphism in intron 16 of the ACE gene was categorized into three genotypes: two deletion alleles (genotype DD), heterozygous alleles (genotype ID), and two insertion alleles (genotype II). The genotype II and I allele frequency were significantly higher in pilots (44.07% and 0.65) than that in healthy subjects (31.25% and 0.52). It is suggested that I gene of ACE may play a role in performance of the pilots.

English Abstract↗

PubMed2001

Genetic susceptibility to multiple sclerosis: detection of polymorphic nucleotides and an intron in the 3' untranslated region of the major histocompatibility complex class II transactivator gene.

The master player in the transcriptional regulation of major histocompatibility (MHC) class II genes is a factor known as the MHC class II transactivator (CIITA). In this study we searched for polymorphisms in the 5' and 3' ends of the human CIITA gene to assess whether or not there is an association between alleles of this gene and multiple sclerosis (MS). Polymorphism screening based upon detection of single strand conformational changes (SSCP analysis) followed by sequencing revealed six single nucleotide variations, namely one in the promoter utilized by B cells and five in the 3' untranslated region (UTR) of the gene. Determination of alleles at these polymorphic sites was facilitated by treatment of amplified DNA fragments with a panel of appropriate restriction enzymes. The distributions of CIITA alleles did not differ between MS patients and control subjects (p > 0.05). After subgrouping of the patients into relapsing-remitting MS and primary progressive MS we found that the distribution of promoter alleles in the latter of these two patient groups differed from that of healthy control subjects (p = 0.04). There was no evidence of linkage disequilibrium between the polymorphic site in the B cell specific promoter and those in the 3' UTR. Based upon the polymorphic sites in the 3' UTR we identified two common CIITA haplotypes which were present at similar frequencies in patients and control subjects. Assuming that susceptibility to MS depends upon type of MHC class II molecule as well as the amounts of expressed class II molecules we tested for interaction between DR15 status and CIITA alleles. No such interaction was detected. Unexpectedly, we identified an intron in the 3' UTR of the human as well as the mouse CIITA gene. Due to the proximity of these introns to the termination codon in both the human and mouse CIITA gene, the mechanism for regulation of transcript stability known as nonsense-mediated decay is probably not involved in the posttranscriptional control of the expression of these genes. So far, the function and significance of the intron in the human and mouse CIITA genes are unknown.

3' Untranslated Regions↗

PubMed2000

Polymorphism of cystic fibrosis gene in Japanese patients with chronic pancreatitis.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the 5T genotype of the polythymidine tract at the exon 9 splice branch/acceptor site are shown to be associated with chronic pancreatitis in Caucasian patients. In contrast to Western countries, cystic fibrosis is extremely rare in Japan. In this study, we investigated the association of mutations or polymorphisms of the CFTR gene with chronic pancreatitis in Japanese patients. Forty-seven patients with chronic pancreatitis (alcohol-related in 31, idiopathic in 14, and familial in 2) were examined for the deltaF508 and R117H mutations and polymorphisms of intron 8. DNA was extracted from leukocytes. Mutations and polymorphisms were examined by the allele-specific polymerase chain reactions and confirmed by direct sequencing. None of the patients had deltaF508 or R117H mutations in the CFTR gene. All of 47 healthy Japanese showed the homozygous 7T/7T genotype, whereas the frequencies of 5T, 7T, and 9T alleles were 0.043, 0.894, and 0.064 in the patients, respectively. The difference in allele frequency is statistically significant. Therefore, the present study indicates the association of polymorphism of the polythymidine tract in intron 8 of the CFTR gene with chronic pancreatitis in Japanese patients.

Adult↗

PubMed2001

Lack of association between alpha2-macroglobulin polymorphisms and Alzheimer's disease.

This study was undertaken to investigate the role of two alpha2-macroglobulin (A2M) polymorphisms, an intronic 5-bp deletion and Ile1000Val, in the development of Alzheimer's disease (AD) and to evaluate the interaction between the apolipoprotein E (APOE) and A2M polymorphisms. The A2M polymorphisms were screened by using polymerase-chain-reaction-based assays in 555 white late-onset AD cases and 446 controls. The gentoype distributions of the 5-bp deletion and Ile1000Val polymorphisms were comparable between cases and controls (P = 0.158 and P = 0.148, respectively). Likewise, there was no significant difference in allele frequencies of each polymorphism among cases and controls (P = 0.361 and P = 0.062, respectively). The stratification of data by APOE*4 status also did not yield any significant association. In conclusion, we observed no association between either the intronic deletion polymorphism or the Ile1000Val polymorphism of A2M and AD in our case-control cohort.

Aged↗

PubMedDate not supplied

Allele frequencies of +874T-->A single nucleotide polymorphism at the first intron of interferon-gamma gene in a group of Italian centenarians.

Ageing is characterized by a pro-inflammatory status which could contribute to the onset of major age-related diseases such as cardiovascular diseases, neurodegeneration, osteoarthritis and osteoporosis, and diabetes. Thus, it can be hypothesized that genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. We have studied the distribution of +874T-->A interferon-gamma (IFN-gamma) polymorphisms in a large number of Italian centenarians to evaluate if the two alleles might be differently represented in people selected for longevity. DNA samples were obtained from 174 Italian centenarians (>99 years old, 142 women and 32 men) and from 248 <60-year-old control subjects (90 women and 158 men) matched for geographical distribution. Polymorphisms at +874 were identified by using amplification refractory mutational system methodology. The +874T allele was found less frequently in centenarian women than in centenarian men or in control women whereas no significant differences were observed in the distribution of the two alleles between male or female controls. Allele frequencies in centenarian men were not found significantly different from male controls. Possession of the +874A allele, known to be associated with low IFN-gamma production, significantly increases the possibility to achieve extended longevity, suggesting that the pro-inflammatory status characteristic of ageing may be detrimental for successful ageing. The datum that the allele was significantly increased in female but not male centenarians seems to strengthen the idea that gender may be a major variable in the biology of the ageing process. However, the present data add another piece of evidence to the complex puzzle of genetic and environmental factors involved in controlling life span expectancy in humans. Thus, studies on cytokine gene polymorphisms may promise to individuate a complex network of trans-interactive genes able to influence the type and strength of responses to environmental stressors and as a final result, thereby conditioning individual life expectancy.

Adult↗

PubMed2001

Fluorescent multiplex polymerase chain reaction analysis of four genes associated with inpaired fibrinolysis and myocardial infarction.

Multiplex polymerase chain reaction (PCR) allows for the simultaneous amplification of several genes, thereby optimizing the use of reagents and decreasing personnel time. Multiplex PCR was used to amplify four genes in one PCR reaction, demonstrating the advantage of multiplex PCR for our study since it allowed us to amplify four separate genes using only 1 microl DNA, thus maximizing the use of study DNA. As compared with conventional multiplex PCR analysis with ethidium bromide, incorporating fluorescence-labeled primers into multiplex PCR reactions facilitated accurate, simultaneous analysis of many DNA fragments within one base discrimination. We have used this fluorescence methodology to analyze polymorphisms associated with either impaired fibrinolysis or myocardial infarction. These include the angiotensin converting enzyme insertion/deletion (I/D) polymorphism in intron 16 of the DCP1 gene, the Alu I/D polymorphism of the tissue plasminogen activator-25 locus in intron 8, the plasminogen activator inhibitor 4G/5G repeat polymorphism, and the variable number tandem repeat of the endothelial cell nitric oxide synthase gene, all characterized by an insertion, deletion, or repeat. The amplified products were diluted 1 : 60 and analyzed on the ABI PRISM 310 Genetic Analyzer using GeneScan software. With this method, we were able to amplify four genes using 75% less reagents and personnel time, thus demonstrating the benefit of multiplex PCR and fluorescence technology.

Alleles↗

PubMed2006

Haplotype analysis of beta-actin gene for its association with sperm quality and boar fertility.

beta-actin (ACTB) was examined as a direct functional candidate gene for the possible association with sperm concentration, motility (MOT), semen volume per ejaculate, plasma droplet rate, abnormal sperm rate (ASR) and the fertility traits, non-return rate and number of piglets born alive (NBA). Three polymorphisms in intron 3 (T>C) and one polymorphism in exon 4 (T>C) of porcine ACTB gene were identified by comparative sequencing of animals of the breeds Pietrain and Hampshire. Association analysis revealed that haplotypes affected the variation of the traits MOT, ASR and NBA. The beneficial haplotypes may provide considerable improvement of sperm quality and fertility in the tested commercial boar population.

Actins↗

PubMed1998

Two novel mutations in exons 19a and 20 and a BsaBI [correction of BsaI] polymorphism in a newly characterized intron of the neurofibromatosis type 1 gene.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. It is caused by mutations in the NF1 gene, which comprises 60 exons and is located on chromosome 17q11.2. A total of 170 unrelated NF1 patients were screened for mutations in four exons by temperature-gradient gel electrophoresis. Preparatory work revealed the presence of a previously uncharacterized intron (19a) in what was previously designated exon 19; this allowed us to develop assays for genomic mutation screening in the newly defined exons 19a and 19b. Two novel NF1 mutations were detected: a single-base insertion in exon 19a creating a frameshift, and a second mutation affecting the splice donor site of intron 20 and leading to skipping of exon 20. A novel BsaBI polymorphism was identified in intron 19a.

Adult↗

PubMed1999

Mutation screening of the tau gene in patients with early-onset Alzheimer's disease.

Hyperphosphorylated microtubule associated protein tau, present in neurofibrillary tangles, is a prominent pathological feature of Alzheimer's disease (AD). The gene encoding tau (MAPT) was recently found mutated in frontotemporal dementia (FTD) and other tauopathies. We studied MAPT as a candidate gene in the etiology of AD. The study population consisted of 101 early-onset AD patients and 117 controls. Mutation analysis did not detect causal mutations in exons 9 to 13 encoding the microtubule-binding domains involved in FTD, however, two novel polymorphisms were detected in exon 9. Using the Ala169 polymorphism in exon 9 and a previously reported (CA)n-repeat polymorphism in intron 9, an association study was performed. No association with early-onset AD was detected. Together, our data indicate that MAPT does not play a role in early-onset AD.

Aged↗

PubMed2001

MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis.

MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by gammadelta T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA-B and TNFalpha. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA-B gene, in patients of Caucasoid origin with Crohn's disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis. We could also not discover any associations of specific two-point or three-point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.

Colitis, Ulcerative↗

PubMed2005

Association of interleukin-I beta and receptor antagonist gene polymorphisms with late onset Alzheimer's disease in Taiwan Chinese.

Interleukin (IL)-1 is markedly overexpressed in the brains of patients with Alzheimer's disease (AD). We aimed to evaluate the relationship between three polymorphisms of the IL1 gene (IL-1beta promoter -511T/C, IL-1beta exon 5 E1/E2 and IL-1-RA) and late onset AD in Taiwan Chinese. Forty-six late onset AD patients and 103 unrelated, age-matched, healthy controls living in the same area were included. PCR was used to resolve the two IL-1beta polymorphisms and the IL-1Ra intron 2 polymorphism. The -511T/T type of the IL-1beta promoter (unlike IL-1beta exon 5 and IL-1-RA) was more frequently found in AD than in healthy patients (-511C/C type versus T/T type, OR = 0.944, CI = 0.393, 2.269, P = 0.898; -511C/T type versus T/T type, OR = 0.375, CI = 0.156, 0.902, P = 0.028). The -511T/T genotype (unlike the other two polymorphisms) is a marker demonstrating that late onset AD in Chinese patients in Taiwan is genetically determined.

Aged↗

PubMed1998

Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders.

The serotonin transporter is a compelling candidate gene to examine in bipolar and unipolar affective disorder, since drugs that specifically inhibit the serotonin transporter can successfully treat depression. Previous association studies of a VNTR polymorphism in intron 2 and a functional insertion/deletion polymorphism in the promoter of this gene have produced conflicting results. The present study examined allele and genotype frequencies for both of these polymorphisms and resulting haplotypes in 87 English Caucasian bipolar patients, 125 English Caucasian unipolar affective disorder patients, and 174 controls. No significant associations were detected when these unipolar or bipolar cases were compared either separately or as a pooled "affective disorder" group to the controls. A meta-analysis of over 1,400 individuals of European Caucasian origin was then performed, comprising 772 controls, 375 bipolar and 299 unipolar patients for the VNTR polymorphism, and 739 controls, 392 bipolar and 275 unipolar patients for the promoter polymorphism. A significant association of promoter allele 2 was shown with bipolar (estimated odds ratio 1.21; 95% confidence interval 1.00-1.45), unipolar (OR 1.23; 95% CI 1.01-1.42), and combined bipolar + unipolar groups (OR 1.22; 95% CI 1.04-1.42). There was no demonstrable allelic association of the VNTR polymorphism with affective disorder: for the combined bipolar + unipolar group the odds ratios for VNTR alleles 9 and 10, compared with the common allele 12 were 1.05 (95% CI 0.56-1.95) and 0.90 (95% CI 0.77-1.05). These results suggest that the promoter allele 2, which has previously been shown to result in lower levels of serotonin transporter transcription, may be associated with affective disorder risk.

Adult↗

PubMed2002

Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease.

Alzheimer's disease (AD) is a complex, multifactorial disorder, with many genetic and environmental factors implicated in disease onset and pathology. Increasing evidence points to a link between brain cholesterol turnover and AD. The CYP46 gene encodes for the enzyme, cholesterol 24-hydroxylase, which plays a key role in brain cholesterol turnover. A polymorphism in Intron 2 (T-->C) in the CYP46 gene has recently been reported to be associated with the risk of AD. In the present study, we examined the association of this CYP46 polymorphism with sporadic late-onset AD (LOAD) in American White (434 cases, 401 controls) and African American (54 cases, 61 controls) cohorts. No significant association was observed between the CYP46 polymorphism and LOAD. When the data were stratified by the apolipoprotein E*4 carrier status, no significant difference was observed between cases and controls for the CYP46 single nucleotide polymorphism. In addition, no significant difference in genotype or allele frequency was observed when stratified by the presence or absence of the alpha1-antichymotrypsin*A allele. Our data indicate that the Intron 2 polymorphism of CYP46 does not affect the risk of AD in our sample.

Age Factors↗

PubMedDate not supplied

p53 intron 2 genotypes detected in normal specimens and lung carcinomas in Hong Kong.

Previous studies suggest that the polymorphic p53 intron 2 displays a high frequency of mutations, occurring with different frequencies in tumor tissues versus peripheral blood of lung cancer patients as compared to healthy individuals. We evaluated the significance of these polymorphisms and mutations utilizing matched triple specimens from the lung tumor, normal lung tissue, and peripheral blood of cancer patients. Identical genotypes were observed in normal tissues and blood, while 4 mutations were observed in tumors. The A1 allelic frequency was increased in the adenocarcinoma tissues as compared to normal tissues. Two p53 exon 2 polymorphisms were detected, appearing with equal frequencies among cancer patients and healthy individuals. The p53 intron 2 polymorphic locus is a hot spot for mutations in Hong Kong lung cancer patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Monoamine oxidases A and B gene polymorphisms in migraine patients.

Abnormal cortical activity and brainstem functioning are considered the possible etiopathogenetic factors of migraine. Monoamine oxidase A and B (MAO-A and -B) regulate the levels of monoamine neurotransmitters, so changes in their activity could participate in migraine pathogenesis. We have investigated the possible association of MAO-A and -B alleles and haplotypes with two common types of migraine, i.e. migraine without aura (MO) and migraine with aura (MA), on the sample of 110 migraineours (80 MO and 30 MA) and 150 controls. MAO-A promoter and MAO-B intron 13 polymorphisms were genotyped by the PCR-based methods. In addition, we have reevaluated the reported association between MAO-B intron 13 polymorphism and platelet MAO-B activity. The platelet MAO-B activity was determined fluorimetrically using kynuramine as a substrate. We have found a tendency toward association of the shorter variant of MAO-A gene promoter with migraine without aura in male subjects. Regarding investigated MAO-B polymorphism, no association with migraine or with platelet MAO-B activity was found. The suggestive association of the variant in MAO-A gene with migraine is considered worthy of independent replication. On the other hand, further studies on MAO-B polymorphism in migraine do not seem promising.

Adult↗

PubMed1999

[A preliminary study on the genetic susceptibility of asthma in a Chinese population].

OBJECTIVE: To study the asthma genetic susceptibility by way of ccandidate region so as to accumulate data on the related loci in Chinese population and determine whether genetic susceptibility to asthma is linked to the chromosome region. METHODS: One hundred ninety-two samples from 32 families were collected from Zhaoan county in Fujian province. Two Rsa I polymorphic sites within uncoded region of the high-affinity IgE receptor beta chain gene (Fc(epsilon) RI-beta) located on chromosome 11q13 were detected by PCR/Rsa I restriction endonuclease digestion. The polymorphic markers D5S436 and D5S393 within chromosome 5q31-33 were amplified by PCR incorporated with radioactive isotope. The asthma family samples were compared with unrelated samples randomly selected from general population. RESULTS: Genotypes containing A allele within intron 2 polymorphic site of Fc(epsilon) RI-beta gene were associated with asthma (P<0.05,OR = 2.039). Significant difference in the level of total serum IgE was noted among three genotypes of intron 2 polymorphic site of Fc(epsilon) RI-beta gene (P<0.05). The association between A allele and elevated total serum IgE was also significant (P<0.05, RR = 1.361). No relationship between exon 7 polymorphic site of Fc epsilonRI-beta gene and asthma was shown. By sib-pair analysis, significant evidence for linkage to asthma was observed with D5S436 (P<0.05) but not with D5S393. No significant linkage to total serum IgE was identified with both of these markers. CONCLUSION: The above-accumulated data suggested that both Fc epsilonRI-beta gene and chromosome 5q31-33 could be very attractive candidate gene and region for further studies in Chinese population, and to confirm these preliminary results, more markers within these regions merit testing in additional population samples.

Adolescent↗

PubMed2003

Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas.

Hypoxic stress at high altitude requires adaptations in several physiological functions to ensure the optimal oxygenation of all cells. Several lines of evidence suggested that high-altitude native populations such as Sherpas have been genetically adapted to their stressful environment. We investigated the genetic variation in the hypoxia-inducible factor (HIF)-1alpha gene in Sherpas as compared with Japanese, native lowlanders, and found a novel dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene. GT15 allele was more frequent in Japanese than in Sherpas with statistical significance, while GT14 allele was significantly more frequent in Sherpas as compared with Japanese. A possible genetic variation in the HIF-1alpha gene might function in adaptation to living at high altitude. Because the activity of HIF-1 is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in intron 13 on the cellular hypoxic responses remains to be elucidated.

Adaptation, Physiological↗