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PubMed2000

MS for identification of single nucleotide polymorphisms and MS/MS for discrimination of isomeric PCR products.

ESI (electrospray ionization) MS and tandem mass spectrometry (MS/MS) were used for the analysis of single nucleotide polymorphisms (SNPs) and more complex genetic variations. Double-stranded (ds) PCR products were studied. PCR products of the proline [5'-x(G17)-x(C38)x-3'] and arginine variants [(5'-x(Gl7)-x(G38)x-3'] of the p53 gene are distinguished by an SNP (cytosine or guanine) and were discriminated using both quadrupole and quadrupole ion trap MS analysis. A 69 bp arginine mutant PCR product [5'-x(C17)-x(G38)x-3'] with a negating switch has the same mass as the proline variant but was readily distinguishable on ion trap MS/MS analysis; fragments containing the mutation site, but not the polymorphism, were identified. The 69 bp PCR products were restriction-enzyme-digested, to create 43 bp fragments. ESI quadrupole ion trap MS/MS analysis of the 43 bp product-ion spectra readily demonstrated both polymorphism and negating switch sites. MS and MS/MS are powerful and complementary techniques for analysis of DNA. MS can readily distinguish SNPs but MS/MS is required to differentiate isomeric PCR products (same nucleotide composition but different sequence).

Mass Spectrometry↗
PubMed1996

Nitric oxide: a modulator for the epidermal growth factor receptor expression in developing ovarian granulosa cells.

the present study was designed to assess the involvement of nitric oxide (NO) in the regulation of the epidermal growth factor (EGF) receptor during development of rat granulosa cells, which were prepared by puncturing ovaries of diethylstilbestrol-treated rats. The immature cells were cultured for 48 h with follicle-stimulating hormone (FSH) to be transformed into mature cells. A marked accumulation of guanosine 3',5' -cyclic monophosphate (cGMP) was observed during development. The accumulation of cGMP, but not of adenosine 3',5'-cyclic monophosphate (cAMP), was suppressed by specific inhibitors of NO synthase, L-NG-monomethyl-L-arginine (L-NMMA) and L-N(G)-nitro-L-arginine, and a selective inhibitor of the inducible NO synthase, aminoguanidine. The L-NMMA-induced suppression was partially reversed by addition of L-arginine to cultures but not D-arginine, indicating that NO formation is inhibited by competing with analogues of L-arginine for NO synthase. Treatment with 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide , an antagonist of NO, caused suppression in the increase of EGF binding sites, whereas exposure of the cells to sodium nitroprusside (SNP), an NO donor, caused elevation in EGF binding sites, with increasing extra- and intracellular cGMP levels. Analysis of the EGF receptor by affinity labeling with 125I-labeled EGF revealed that the intensity of the cross-linked receptor molecular with a molecular mass of 180 kDa was increased by exposure to SNP. The facilitatory effect of SNP on the EGF receptor was observed when the cAMP-dependent pathway was fully activated by FSH. However, the NO effect may be mediated by a cGMP-independent pathway, as 8-bromo-cGMP did not mimic the action of SNP. These results indicate that the L-arginine-NO system may contribute to the regulation of EGF receptor expression in developing granulosa cells stimulated by FSH.

Animals↗
PubMed2002

[Linkage disequilibrium analysis of the single nucleotide polymorphisms in the PRKCZ gene].

OBJECTIVE: To search for the disease-associated haplotype in the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, by case-control study and linkage disequilibrium (LD) analysis using single nucleotide polymorphisms (SNPs). METHODS: SNPs located in the PRKCZ gene were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method was used to genotype the loci in 173 sporadic type 2 diabetes patients and 152 normal individuals to perform case-control study and LD analysis. Haplotype block were constructed in these populations. RESULTS: Several SNPs in the PRKCZ gene were found to be associated with the disease. The SNPs formed different haplotype block pattern in case and control groups. The frequencies of the haplotypes formed by 5 SNPs were statistically different between the two groups. CONCLUSION: The haplotype formed by 5 SNPs in the PRKCZ gene may be associated with type 2 diabetes in Han population of China, which is confirmed from statistics to be a susceptibility gene for the disease.

Alleles↗
PubMed2006

The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B.

Surfactant protein B (SP-B) is an essential component of surfactant that promotes adsorption and spreading of surfactant phospholipids and stabilizes the phospholipid monolayer. SP-B is essential for respiratory function in newborn humans and mice; adult mice with levels of SP-B below 25% of wild-type develop fatal respiratory distress syndrome. A potential regulatory function of the C/A(-18) single nucleotide polymorphism (SNP) in the promoter of the SP-B gene was examined. Transcriptional analysis and ELISA on bronchoalveolar lavage fluid revealed that the presence of the C allele correlated with more SP-B promoter activity and protein. There was approximately threefold difference in amounts of SP-B in bronchoalveolar lavage fluid from CA(-18) and AA(-18) individuals. By EMSA, Sp1 bound more tightly to the C allele sequence than to the A allele sequence, perhaps accounting for the differences in transcription. Genotyping of a normal volunteer population showed approximately 31% of the population were AA homozygotes, suggesting that these individuals produce less SP-B. Differences in amounts of SP-B resulting from the promoter SNP could affect the clinical presentation of pulmonary disease.

Adenine↗
PubMed2002

Tumour necrosis factor receptor II polymorphism and juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a complex polygenic disorder. The encouraging outcome of anti-tumour necrosis factor (TNF) treatment, as well as serological studies, has implicated TNF and its receptors (TNFRI and TNFRII, or TNFRSF1B) in the pathogenesis of JIA. The purpose of this study was to investigate the exon 6 TNFRII single nucleotide polymorphism (SNP) in a well-defined UK cohort of JIA patients, using case-control association analysis. METHODS: A total of 435 patients, spanning seven JIA subgroups, and 261 healthy individuals were screened for the polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No significant differences were observed between the SNP allelic or genotypic frequencies of patients and controls, or between JIA subgroups. CONCLUSIONS: This TNFRII exon 6 SNP does not seem to be associated with susceptibility to JIA.

Antigens, CD↗
PubMed2004

ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics.

BACKGROUND: A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population. OBJECTIVE AND METHODS: To assess whether genetic variants of ADAM33 are related to asthma in a Korean population, we conducted an association study of the ADAM33 gene with asthma susceptibility, bronchial hyper-reactivity and serum IgE in Korean asthmatics (n=326) and normal controls (n=151). Five of the 14 polymorphisms originally reported to be associated with asthma development (S1 G>A, T1 T>C, V-1 C>A, V1 T>A, V4 C>G) were genotyped using single base extension and electrophoresis. Haplotypes and their frequencies were inferred using the algorithm implemented by the software Arlequin. Allele frequencies of each SNP and haplotypes were compared between the patients and the normal controls using logistic regression analysis. RESULTS: There was no significant difference in the distribution of SNPs and the six haplotypes between asthmatics and normal controls. All single SNPs and six haplotypes in ADAM33 were also analysed for the association with level of PC(20) using general linear models. The distribution of the T1 T>C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC(20) methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model). CONCLUSION: Polymorphism of ADAM33 may contribute to development of BHR in asthma.

ADAM Proteins↗
PubMed2006

Multiple candidate gene analysis identifies alpha-synuclein as a susceptibility gene for sporadic Parkinson's disease.

Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case-control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case-control populations, we found that a SNP in alpha-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0 x 10(-10)). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D'>0.9) spanning approximately 120 kb. A tight LD group (r2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0 x 10(-9)-1.7 x 10(-11)). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated with the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.

Adult↗
PubMed1986

Skeletal muscle oxygen pressure fields during controlled hypotension with adenosine and sodium nitroprusside. A comparative study in the rabbit.

The MDO (Mehrdraht Dortmund Oberfläche) multiwire oxygen electrode was used for studies of oxygen pressure fields in eight rabbit skeletal muscle preparations during controlled hypotension with adenosine and sodium nitroprusside (SNP). Tissue oxygen histograms were constructed from 120 simple tissue oxygen pressures (PtO2) samples that were collected during 5 min. Statistical analysis between histograms was performed with the two-sample Kolmogorov-Smirnov test. Mean arterial blood pressure was reduced to 60 mmHg with both drugs, corresponding to a 42-43% reduction during the 25-min hypotension period. SNP-induced hypotension caused significant reduction of muscle oxygenization (compared to normotensive controls) in six of the animals, while this occurred on three occasions during adenosine administration. When comparing the histograms during hypotension, the tissue oxygenation during adenosine infusion was higher than during SNP in five and equal to SNP in three animals. Low tissue oxygen pressure values (0-0.6 kPa) were four times more frequent during SNP than during adenosine hypotension, although systemic arterial oxygen pressures were unaffected. We conclude that controlled hypotension with adenosine preserves tissue oxygen pressures better than hypotension induced by SNP.

Adenosine↗
PubMed2006

Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives.

To identify low penetrance susceptibility alleles for colorectal cancer (CRC), we genotyped 1467 non-synonymous SNPs mapping to 871 candidate cancer genes in 2575 cases and 2707 controls. nsSNP selection was biased towards those predicted to be functionally deleterious. One SNP AKAP9 M463I remained significantly associated with CRC risk after stringent adjustment for multiple testing. Further SNPs associated with CRC risk included several previously reported to be associated with cancer risk including ATM F858L [OR=1.48; 95% confidence interval (CI): 1.06-2.07] and P1054R (OR=1.42; 95% CI: 1.14-1.77) and MTHFR A222V (OR=0.82; 95% CI: 0.69-0.97). To validate associations, we performed a kin-cohort analysis on the 14 704 first-degree relatives of cases for each SNP associated at the 5% level in the case-control analysis employing the marginal maximum likelihood method to infer genotypes of relatives. Our observations support the hypothesis that inherited predisposition to CRC is in part mediated through polymorphic variation and identify a number of SNPs defining inter-individual susceptibility. We have made data from this analysis publicly available at http://www.icr.ac.uk/research/research_sections/cancer_genetics/cancer_genetics_teams/molecular_and_population_genetics/software_and_databases/index.shtml in order to facilitate the identification of low penetrance CRC susceptibility alleles through pooled analyses.

Aged↗
PubMed2005

Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries.

OBJECTIVE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis. This study investigates the effects of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. METHODS: The coronary arteries were harvested from pig hearts and cut into 5-mm ring segments, which were then divided into six groups, including control, Hcy alone (50 microM), low-dose (1 microM) or high-dose (10 microM) Rb1 alone, and Hcy plus low-dose or high-dose Rb1. After 24-hour incubation, the rings were analyzed for vasomotor function in response to thromboxane A2 analog U46619, bradykinin, and sodium nitroprusside (SNP), respectively. In addition, superoxide anion was assessed by lucigenin-enhanced chemiluminescence analysis. Endothelial nitric oxide synthase (eNOS) was studied using real-time polymerase chain reaction and Western blot. RESULTS: Endothelium-dependent relaxation (bradykinin) was significantly reduced in rings treated with Hcy alone as compared with the control (49.80% vs 71.77%, n = 8, P < .05), whereas neither high-dose nor low-dose Rb1 alone affected the endothelium-dependent relaxation. The low-dose Rb1-Hcy combined group had a partially improved endothelium-dependent relaxation (54.44%), whereas the high-dose Rb1-Hcy combined group showed a complete recovery of endothelium-dependent relaxation (72.89%). There was no substantial difference in maximal contraction induced by U46619 or endothelium-independent relaxation by SNP among all groups (P > .05). Furthermore, superoxide anion was markedly increased by 137% in the Hcy-treated group as compared with the control, but there were no statistically significant changes from the control in all other groups (P > .05). Lastly, eNOS mRNA and protein levels were substantially reduced in the Hcy-treated group, but not in the Rb1-Hcy combined groups. CONCLUSIONS: This is the first study to show that ginsenoside Rb1 can effectively block Hcy-induced endothelial dysfunction and superoxide anion production as well as eNOS downregulation in porcine coronary arteries. This study suggests that ginseng and its active constituents may have potential clinical applications in controlling Hcy-associated vascular injuries. CLINICAL RELEVANCE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis and other vascular lesions. It causes endothelial dysfunction and oxidative stress. Ginseng compounds have effects of vasorelaxation and antioxidation. The purpose of this study was to determine the effect of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. Our results showed that ginsenoside Rb1 can effectively block Hcy-induced dysfunction of endothelium-dependent vasorelaxation as well as superoxide anion production and eNOS downregulation. This study suggests that ginseng compounds may have potential clinical applications in controlling Hcy-associated vascular diseases and other vascular lesions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Sequence characterization, tissue-specific expression and polymorphism of the porcine (Sus scrofa) liver-type fatty acid binding protein gene.

In this study, the full-length cDNA of porcine liver-type fatty acid binding protein gene (L-FABP) was obtained by the rapid amplification of cDNA ends (RACE). The nucleotide sequence and the predicted protein sequence share a high sequence identity with their mammalian counterparts. Semi-quantitative RT-PCR revealed that porcine L-FABP gene is expressed in all twelve tissues studied, but a transcript is more abundant in liver and small intestine than in other tissues. The part genomic DNA of the porcine L-FABP gene was amplified by PCR. The coding region of the pig L-FABP gene is organized in four exons and spans an approximate 2.62 kb genomic region. Comparative sequencing of four pig breeds revealed a C-->T single nucleotide polymorphism (SNP) within exon 2. The allele and genotype frequencies differed significantly between indigenous Chinese Zang, Dahe, and Yanan pigs with higher frequencies of allele C and genotype CC and Yorkshire pigs with higher frequencies of allele T and genotype TT (P < 0.01). The association analysis suggested that the C-->T polymorphism was associated with intramuscular fat content, indicating that the SNP is a potential molecular marker for intramuscular fat content.

Amino Acid Sequence↗
PubMed1998

Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature.

OBJECTIVES: This study sought to define the local regulation of vascular tissue-type plasminogen activator (t-PA) release. BACKGROUND: The vascular endothelium, through the production of t-PA and plasminogen activator inhibitor (PAI-1), is an important regulator of fibrinolysis. Plasma t-PA levels increase in response to adrenergic stimulation; however, it is unclear whether this increase is the result of systemic reflex responses or direct effects on the vascular endothelium. METHODS: Forearm blood flow dose responses were generated to low doses of agonist infused directly into the brachial artery in 15 normotensive men (mean [+/-SE] age 28.9 +/- 2.2 years). Simultaneous arterial and venous blood samples were drawn at baseline and in response to the intraarterial administration of isoproterenol (400 ng/min), methacholine (8 microg/min) and sodium nitroprusside (SNP) (8 microg/min). PAI-1 and t-PA antigen levels were measured by enzyme-linked immunosorbent assay, and the net release across the forearm was calculated. RESULTS: Forearm plasma flow increased significantly from baseline (1.4 +/- 0.2 ml/100 ml per min) after administration of isoproterenol, methacholine and SNP (9.7 +/- 1.9, 8.7 +/- 1.9 and 6.7 +/- 1.1 ml/100 ml per min, respectively) (p < 0.001 by analysis of variance). Baseline net t-PA release (0.7 +/- 0.3 ng/100 ml per min) increased significantly after administration of isoproterenol (26.2 +/- 11.6 ng/100 ml per min, p = 0.005) and methacholine (15.3 +/- 5.5 ng/100 ml per min, p = 0.001) but not after administration of SNP (1.8 +/- 2.2 ng/100 ml per min, p = 0.84). There was no net release of PAI-1 across the vascular bed. CONCLUSIONS: Marked, rapid local t-PA release occurred in response to isoproterenol, a beta-adrenoceptor agonist, and methacholine, an endothelium-dependent nitric oxide agonist, in the human forearm. This effect was selective and independent of the effects of shear stress due to increased flow because SNP induced similar increases in forearm blood flow without affecting t-PA release. Vascular t-PA release may be a potentially valuable tool for evaluating endothelial function in diseases associated with increased risk of thrombosis.

Adult↗
PubMed2005

Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk: strong confirmation of functional promoter SNP.

The E-cadherin gene (CDH1) has been proposed as a prostate cancer (PC) susceptibility gene in several studies. Aberrant protein expression has been related to prognosis and progression in PC. In addition, a functional promoter SNP (rs16260) has been found to associate with PC risk. We performed a comprehensive genetic analysis of CDH1 by using the method of haplotype tagged SNPs in a large Swedish population-based case-control study consisting of 801 controls and 1,636 cases. In addition, Swedish PC families comprising a total of 157 cases sampled for DNA were analyzed for selected SNPs. Seven SNPs, including the promoter SNP rs16260, that captured over 96% of CDH1 haplotype variation were selected as haplotype tagging SNPs and analyzed for associated PC risk. We observed significant confirmation of rs16260 (P=0.003) for cases with a positive family history of PC (FH+) both in an independent case-control population and in PC families. In addition, a common haplotype (HapB, 25%) including the variant allele of rs16260 was associated (P=0.004) with PC risk among FH+ cases. The promoter SNP rs16260 as well as HapB were significantly transmitted to affected offspring in PC families. We report strong confirmation of the association between PC risk in FH+ cases and a functional CDH1 promoter SNP in an independent population. In conjunction with the biological importance of CDH1 our findings encourage further evaluation of genetic variation in CDH1 in relation to PC etiology. Due to the difficulties in replication of genetic association studies, this finding is unusual and novel.

Adult↗
PubMed2005

Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population.

OBJECTIVE: To identify rheumatoid arthritis (RA) susceptibility genes in a Japanese population by conducting a large-scale case-control association analysis and linkage disequilibrium (LD) mapping on chromosome 7q31-34, a candidate susceptibility locus identified in a preliminary genome-wide scan in 53 Japanese families, using single-nucleotide polymorphisms (SNPs). METHODS: We prepared 728 dense, evenly spaced SNPs with a minor allele frequency >0.15 in each gene locus on chromosome 7q31-34. Using these SNPs, a 2-stage case-control analysis was performed on 760 RA patients (157 men and 603 women) and 806 non-RA controls (189 men and 617 women). Haplotypes and LD mapping results were assessed based on SNP genotypes in 380 controls. RESULTS: Forty-eight SNPs showed allele associations (P < 0.05) in the first set of DNA samples (380 RA cases and 380 non-RA controls; first-stage analysis). For 4 of the SNPs in the SEC8L1 gene, the association was replicated (P < 0.05) in the second, independent set of DNA samples (an additional 380 RA cases and 380 non-RA controls; second-stage analysis). When data from the 2 groups were combined, the most significant allele association was observed with SNP 441, an intronic SNP of the SEC8L1 gene (P = 0.000059). The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4). Haplotype analysis revealed the disease-risk (P = 0.0015) and disease-protective (P = 0.0000062) haplotypes. Resequencing of coding exons within block 4 did not identify any nonsynonymous SNPs. Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients. CONCLUSION: Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA. We propose that SEC8L1, which encodes a component of the exocyst complex, is a candidate susceptibility gene for RA in the Japanese population.

Adult↗
PubMed2005

DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters.

ADHD is one of the most prevalent, and heritable behavioural disorders in childhood. Genetic associations have been reported with polymorphic variants within or near to dopamine pathway genes. Recently snap-25 has also shown association with ADHD in several datasets. We therefore investigated other genes that produce proteins that interact with SNAP-25 in the mechanism of vesicular release of neurotransmitters at the synapse. A total of 106 SNPs were screened for minor allele frequency greater than 5% and 61 SNPs selected for analysis in DNA pools made up from an ADHD clinical sample of DSM-IV combined type probands (n = 180) and a control sample of 90 males and 90 females. Initial screening identified several SNPs that showed allele frequency differences of 5% or more. One SNP in the synaptophysin gene showed suggestive evidence of association following case-control and TDT analysis and warrants further investigation.

Attention Deficit Disorder with Hyperactivity↗
PubMed2007

Triplet repeat in the Repin1 3'-untranslated region on rat chromosome 4 correlates with facets of the metabolic syndrome.

BACKGROUND: Congenic and subcongenic rat strains confirmed the quantitative trait loci (QTLs) for facets of the metabolic syndrome between 60.53 and 77.11 Mb on chromosome 4. The analysis of candidate genes in this region favoured the replication initiator 1 (Repin1) characterized by a SNP in the coding region and a triplet repeat (TTT) in the 3'-untranslated region (3'UTR). METHODS: We analysed nine rat strains (BB/OK, SHR, F344, BN, DA, LEW, hHTg, WOKW, and their founders WOK-F) and four wild rats on DNA (sequencing) and RNA level (gene expression in blood, liver, subcutaneous, and epididymal adipocytes). In addition, the rats were phenotypically characterized in order to link the rat phenotype to genotype differences in the QTL on chromosome 4. RESULTS: Wild rats were heterozygous for the SNP (C/T), whereas all the inbred strains were homozygous. The shortest triplet repeat was found in SHR (5) and the highest was found in hHTg and WOKW (11), which developed metabolic disorders. The repeat number correlated with most phenotypic traits studied. Using linear multiple regression analysis with repeat size as the dependent variable and considering all the data of this study, it was clearly demonstrated that not only VLDL cholesterol and serum insulin but also the expression of Repin1 in the liver is significantly associated with the repeat size of the 3'UTR. CONCLUSIONS: It is concluded that the triplet repeat expansion in 3'UTR is involved in metabolic alterations as found in hHTg and WOKW rats and that the functional unknown gene, Repin1, could be a novel candidate gene for the development of facets of the metabolic syndrome.

3' Untranslated Regions↗
PubMed2004

[Study on the correlation of interleukin-13 polymorphism and susceptibility to chronic obstructive pulmonary disease in Chinese Han population].

OBJECTIVE: To investigate the polymorphism of interleukin (IL)-13 gene in Chinese Han population, and to study the possible association of IL-13 polymorphism and the susceptibility to chronic obstructive pulmonary disease (COPD). METHODS: Using genomic DNA extracted with phenol:chloroform:isoamyl alcohol from the blood of 94 healthy smokers and 88 COPD smokers, three single nucleotide polymorphism (SNP) sites in IL-13 gene marked as 1103C/T, 4257G/A, 4738G/A were determined by polymerase chain reaction/restriction fragment length polymorphism analysis or polymerase chain reaction/single strand conformation analysis. In addition, plasma IL-13 concentration was measured by ELISA on 24 healthy smokers and 24 smokers with chronic obstructive pulmonary disease. RESULTS: (1) To 4257G/A and 4738G/A SNP sites, the genotype frequencies and allele frequencies were not significantly different between healthy smokers and COPD smokers (P > 0.1). (2) To 1103C/T SNP site, relative higher CC genotype frequency and C allele frequency were found in healthy smokers (P < 0.05), also C allele could prevent smokers from chronic obstructive pulmonary disease, with OR 0.56 and 95% confidence interval was 0.34 - 0.91. (3) Plasma IL-13 concentration was not affected by genotype of 4257G/A or 4738G/A SNP sites. However, 1103CC showed for significantly lower IL-13 concentration in plasma (P < 0.05). CONCLUSION: The genotype of IL-13 1103C/T SNP site was associated with the susceptibility to COPD in Chinese Han population and 1103CC accounted for relative lower plasma IL-13 concentration and lower risk for COPD.

Aged↗
PubMed2005

Higher prevalence of OCA1 in an ethnic group of eastern India is due to a founder mutation in the tyrosinase gene.

PURPOSE: Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment and associated with common developmental abnormalities of the eye. It is one of the major causes of childhood blindness in India. The disease is common among an ethnic group (Tili) of Eastern India, which represents about 12.56% of the Bankura district population (approximately 0.4 million) of West Bengal. The purpose of the study was to investigate the molecular lesions causing OCA within this ethnic group for the unequivocal diagnosis of the carriers and attempt to decipher the cause for the high prevalence of OCA. METHODS: Fourteen OCA-affected Tili families consisting a total of 161 individuals, including 26 patients, were recruited for the study. A lack of tyrosinase (TYR) activity among all the patients was ascertained by the tyrosinase hair bulb assay. Mutation screening in the tyrosinase gene (TYR) was done by single strand conformational polymorphism (SSCP) and DNA sequencing. The restriction fragment length polymorphism (RFLP) assay was carried out to determine the frequency of the pathogenic changes among the normal individuals. Haplotype analysis was performed at the TYR locus using a set of informative microsatellite and SNP markers. RESULTS: All the patients were homozygous for a null mutation (c.832C>T, Arg278stop) in TYR exon 2, which might cause a complete loss of enzyme activity. The mutation occurred in the same haplotype background. The frequency of the disease in this ethnic group was estimated to be significantly higher than the world average. CONCLUSIONS: OCA1 in the Tili population is due to the occurrence of a founder mutation in the TYR as indicated by haplotype analysis. Higher prevalence of the mutation in the population group is due to marriage within the same community. The diagnostic RFLP assay can be utilized for genetic counseling and thereby will help to reduce the disease load on the population.

Albinism, Oculocutaneous↗