Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “single nucleotide polymorphisms”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,585 records · Page 88Linked to original sources
PubMed2006

The single nucleotide polymorphism IVS1+309 in mouse double minute 2 does not affect risk of familial breast cancer.

The mouse double minute 2 (MDM2) oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumor suppressor protein. Further, MDM2 overexpression can inhibit DNA double-strand break repair in a p53-independent manner. Recently, it was shown that a single nucleotide polymorphism (SNP) in the MDM2 promoter was associated with an accelerated tumor formation in individuals with a p53 mutation. The present case-control study investigated the association of this SNP (IVS1+309) with the risk and the age of onset of familial breast cancer in patients with unknown p53 mutation status. Data from 549 women affected by familial breast cancer and 1,065 healthy controls were analyzed. The cases did not carry BRCA1/2 mutations. Cases and controls showed a similar genotype distribution and the SNP did not seem to modify the age of onset of familial breast cancer. The data were also examined taking into account the presence of any additional cancer after breast cancer and the family history of cases; however, no association was found. These results suggest that the SNP IVS1+309 alone affects neither the risk nor the age of onset of heritable breast cancer.

Adult↗
PubMed2005

Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and after gastric banding surgery.

BACKGROUND: Certain adipose-produced signals are secreted in proportion to body fat mass and are involved in regulation of the energy metabolism of the whole body. Leptin, IL6 and adiponectin can be considered as adiposity signals. Several Single Nucleotide Polymorphisms (SNPs) in genes encoding for these molecules are known to influence their concentration in situations of stable weight. We hypothesized that polymorphism effects could be better detected in a situation of negative energy balance and that modified concentrations of adiposity signal genes could change the dynamics of weight gain in obese subjects. METHODS: 65 obese patients undergoing gastric banding surgery were genotyped for LEP+19A-->G, LEP-2548G-->C, IL6-174G-->C, APM1-11377C-->G and PM1-11391G-->A common SNPs. BMI and concentrations of leptin, IL6 and adiponectin were measured before surgery and after 1 year. RESULTS: All SNPs except IL6-174G-->C SNP were associated with modifications of the circulating concentrations of signals produced by adipose tissue at baseline. During weight loss, variant genotype carriers of LEP -2548 and +19 SNPs were characterized by a trend towards less decrease in circulating leptin. Weight loss was associated with an increase in IL6 concentration (16.9%+/-12.2) in the IL6-174 C/C genotype carriers, whereas the C/G or G/G genotypes carriers showed a decrease in IL6 (19.9%+/-5.2, P=0.001). CONCLUSION: We observed that the SNPs studied could modulate the concentration of adiposity signals not only at baseline but also during weight loss. Such variations may be sensed by the homeostatic feedback system that controls energy balance and may in turn contribute to some disturbances in weight regulation.

Adiponectin↗
PubMed2004

Matrix metalloproteinase-9 coding sequence single-nucleotide polymorphisms in caucasians with intracranial aneurysms.

OBJECTIVE: There are several lines of evidence suggesting that matrix metalloproteinases (MMPs), particularly MMP-9, are involved in the pathogenesis of intracranial aneurysms. Some studies have demonstrated that genetic variants in the promoter region of the MMP-9 gene are associated with aneurysms. We performed a case-control study to investigate whether single-nucleotide polymorphisms (SNPs) within the coding region of the MMP-9 gene might affect the development of intracranial aneurysms. METHODS: All 13 exons and the 3' untranslated region of the MMP-9 gene were analyzed by direct sequencing in a study group that comprised 40 Caucasian patients with at least one intracranial aneurysm and 44 Caucasian controls. Genotypes were determined, and those that were in Hardy-Weinberg disequilibrium were analyzed in another sample of 40 cases and 40 controls. Differences among the genotype frequencies of the identified polymorphisms were investigated. RESULTS: Seven SNPs were identified in the coding region, two were identified in the adjacent intronic sequences, and two were identified in the 3' untranslated region. Genotype frequencies of four SNPs were demonstrated to be in Hardy-Weinberg disequilibrium in both analyzed study samples. Therefore, an accurate estimation of haplotype frequencies was not possible. No difference in genotype frequencies between cases and controls was detected at any of the 11 SNPs. CONCLUSION: SNPs of the coding region and the 3' untranslated region of the MMP-9 gene are not associated with intracranial aneurysms in Caucasians.

3' Untranslated Regions↗
PubMed2005

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Disease Susceptibility↗
PubMed2007

Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese.

OBJECTIVE: Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of prebeta-high-density lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D. METHODS: Single nucleotide polymorphisms (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non-diabetic control subjects were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Single marker analysis for SNP T-778C indicated that T2D patients had increased frequency of C allele in comparison with non-diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non-diabetic controls, the carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T-778C variant independently of the haplotype context. CONCLUSION: The present study provided the first evidence that SNP T-778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D among Han Chinese.

Aged↗
PubMed2007

Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity.

CONTEXT: Genetic factors are important for the development of obesity. However, the genetic background of obesity still remains unclear. OBJECTIVE: Our objective was to search for obesity-related genes using a large number of gene-based single-nucleotide polymorphisms (SNPs). DESIGN AND SETTING: We conducted case-control association analyses using 94 obese patients and 658 controls with 62,663 SNPs selected from the SNP database. SNPs that possessed P < or = 0.02 were further analyzed using 796 obese and 711 control subjects. One SNP (rs3764220) in the secretogranin III (SCG3) gene showed the lowest P value (P = 0.0000019). We sequenced an approximately 300-kb genomic region around rs3764220 and discovered SNPs for haplotype analyses. SCG3 was the only gene within a haplotype block that contained rs3764220. The functions of SCG3 were studied. PATIENTS: Obese subjects (body mass index > or = 30 kg/m(2), n = 890) and control subjects (general population; n = 658, body mass index < or = 25 kg/m(2); n = 711) were recruited for this study. RESULTS: Twelve SNPs in the SCG3 gene including rs3764220 were in almost complete linkage disequilibrium and significantly associated with an obesity phenotype. Two SNPs (rs16964465, rs16964476) affected the transcriptional activity of SCG3, and subjects with the minor allele seemed to be resistant to obesity (odds ratio, 9.23; 95% confidence interval, 2.77-30.80; chi(2) = 19.2; P = 0.0000067). SCG3 mRNA and immunoreactivity were detected in the paraventricular nucleus, lateral hypothalamic area, and arcuate nucleus, and the protein coexisted with orexin, melanin-concentrating hormone, neuropeptide Y, and proopiomelanocortin. SCG3 formed a granule-like structure together with these neuropeptides. CONCLUSIONS: Genetic variations in the SCG3 gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion.

Adult↗
PubMed2006

The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study.

Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.

Adiponectin↗
PubMed2003

Tumor necrosis factor-alpha gene (TNF-alpha) -1031/-863, -857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese.

OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) participate in the establishment of inflammatory lesions in periodontitis. High production of these cytokines may relate to the severity of periodontitis. There have already been several studies examining the association between periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine productivity. Recently, new SNPs of TNF-alpha, -1031, -863 and -857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high TNF-alpha production. For a better understanding of the genetic factors associated with the severity of periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on TNF-alpha or IL-1beta SNPs associated with periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe periodontitis in Japanese and the following SNPs: five in the TNF-alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta gene (-511, -31, +3953). MATERIAL AND METHODS: A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe adult periodontitis and 64 healthy subjects. TNF-alpha and IL-1beta SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism for all subjects. TNF-alpha and IL-1beta production from LPS-stimulated monocytes/macrophages was also measured for 15 healthy male subjects. RESULTS: TNF-alpha production in TNF-alpha-1031/-863 (linkage disequilibrated) or -857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs among severe periodontitis patients was significantly higher than in healthy subjects. CONCLUSION: Since the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs was higher in periodontitis patients than in healthy subjects, TNF-alpha-1031, -863 and -857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

Alleles↗
PubMed2005

A model of prediction system for adverse cardiovascular reactions by calcineurin inhibitors among patients with renal transplants using gene-based single-nucleotide polymorphisms.

The application of pharmacogenomic information to diagnostic assays is expected to improve the prediction of drug efficacy and toxicity, leading to appropriate therapeutic regimens for individual patients. Cardiovascular events are common and severe adverse drug reactions (ADRs) among transplant patients treated with calcineurin inhibitors (CNIs). We conducted case-control association studies using 50,947 gene-based single-nucleotide polymorphisms (SNPs) to identify genetic variations that might be associated with cardiovascular risk factors in 72 renal transplant recipients with CNI therapy. The overall incidence of cardiovascular events was 13.9% (10/72) among patients receiving cyclosporine or tacrolimus; arrhythmias in six patients (8.3%), ischemic heart diseases in two patients (2.8%), and heart failure in two patients (2.8%). On the basis of results of the genome-wide association studies, we attempted to establish a scoring system to predict individual risks for cardiovascular toxicity of cyclosporine and tacrolimus. Estimation of the predictive performance was carried out by the use of internal leave-one-out cross-validation test. When we combined arrhythmia, ischemic heart disease and heart failure cases as subjects with a cardiotoxicity phenotype, nine of ten ADR patients and 50 of 62 non-ADR patients were correctly classified into the respective categories using the top eight SNPs. In addition, the proportion of individuals in the control population (n=246) with scores over the cut-off (11.0%) was close to the cardiovascular ADR frequency (8.3%) among renal transplant patients in the previous clinical study. Our results open the possibility that prediction of CNI-induced cardiovascular complications can lead to better prognosis and quality of life among kidney-transplant patients, and to improved immunosuppressive regimens.

Calcineurin Inhibitors↗
PubMed2004

Association of the T allele of an intronic single nucleotide polymorphism in the colony stimulating factor 1 receptor with Crohn's disease: a case-control study.

BACKGROUND: Polymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohn's disease. Identification of the remaining Crohn's susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohn's susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity. METHODS: Patients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohn's disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohn's disease and controls with a polyclonal antibody raised against the human CSF1R protein. RESULTS: A single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohn's disease but in only 13% of controls (X2 = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections. CONCLUSIONS: We conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohn's disease.

Journal Article↗
PubMed2004

beta2-adrenergic receptor gene single-nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden.

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein-coupled receptors and is present on skeletal and cardiac muscle cells and on lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population and the distributions of single-nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164 are changed in asthma, obesity, and hypertension and in the autoimmune disease myasthenia gravis. An involvement of the beta2-AR has also been suggested in human rheumatoid arthritis (RA) and its animal model. We describe here an increased prevalence of the alleles Arg16 and Gln27 and a lower prevalence of homozygosis for Gly16 and Glu27 in patients with RA. Patients having the genotype combination GlyGly16-GlnGlu27 had higher levels of rheumatoid factor (RF) and a more active disease than other patients. Patients having the genotype Arg16-Gln27+ had higher levels of RF when compared to those having Arg16+Gln27+, and patients who were carriers of Gln27 had a more active disease than non-carriers of Gln27. Our results show an association of beta2-AR SNPs with RA in a population from the northern part of Sweden. Our study also confirms the strong linkage disequilibrium of genotypes at amino acid positions 16 and 27.

Adult↗
PubMed2006

Genome-wide association study to identify single-nucleotide polymorphisms conferring risk of myocardial infarction.

Myocardial infarction (MI) is characterized by abrupt occlusion of coronary artery resulting in irreversible damage to cardiac muscle. This disease might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by themselves. To reveal the genetic bases of MI, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-alpha gene located on chromosome 6p21 conferred susceptibility to MI. This chapter describes a detailed protocol for performing a genome-wide association study as used in our MI study.

Case-Control Studies↗
PubMed2002

Homozygosity for multiple contiguous single-nucleotide polymorphisms as an indicator of large heterozygous deletions: identification of a novel heterozygous 8-kb intragenic deletion (IVS7-19 to IVS15-17) in a patient with glycogen storage disease type II.

Current methods for detection of mutations by polymerase chain reaction (PCR) and sequence analysis frequently are not able to detect heterozygous large deletions. We report the successful use of a novel approach to identify such deletions, based on detection of apparent homozygosity of contiguous single-nucleotide polymorphisms (SNPs). The sequence analysis of genomic DNA PCR products containing all coding exons and flanking introns identified only a single heterozygous mutation (IVS18+2t-->a) in a patient with classic infantile-onset autosomal recessive glycogen storage disease type II (GSDII). Apparent homozygosity for multiple contiguous SNPs detected by this sequencing suggested presence of a large deletion as the second mutation; primers flanking the region of homozygous SNPs permitted identification and characterization by PCR of a large genomic deletion (8.26 kb) extending from IVS7 to IVS15. The data clearly demonstrate the utility of SNPs as markers for large deletions in autosomal recessive diseases when only a single mutation is found, thus complementing currently standard DNA PCR sequence methods for identifying the molecular basis of disease.

Amino Acid Sequence↗
PubMed2003

Lack of association between TrkA single nucleotide polymorphisms and sporadic Alzheimer's disease in a Japanese population.

Nerve growth factor and its receptor with tyrosine kinase activity (TrkA) have been implicated in the development of Alzheimer's disease (AD). Entire coding regions of TrkA gene harboring exons 1 through 17 were sequenced in 114 patients with sporadic AD and 112 control subjects in a Japanese population, and six known and two novel single nucleotide polymorphisms were identified, but no mutation associated with sporadic AD was identified. Concurrently, case-control analysis of TrkA gene A1674G polymorphism in 534 patients with sporadic AD and 454 control subjects has revealed no significant differences in TrkA genotype or allele frequencies even after stratification for Apolipoprotein E epsilon4 carrier statuses. Thus, the TrkA genotype does not appear to influence the risk of developing sporadic AD in a Japanese population.

Age of Onset↗
PubMed2006

Pyrosequencing, a high-throughput method for detecting single nucleotide polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum.

A pyrosequencing protocol was developed as a rapid and reliable method to identify the mutations of the dhfr and dhps genes of Plasmodium falciparum that are associated with antifolate resistance. The accuracy and specificity of this method were tested using six laboratory-cultured P. falciparum isolates harboring known single nucleotide polymorphisms (SNPs) in the genes dhfr (codons 50, 51, 59, 108, and 164) and dhps (codons 436, 437, 540, 581, and 613). The lowest threshold for detection of all the SNPs tested by pyrosequencing was the equivalent of two to four parasite genomes. Also, this method was highly specific for P. falciparum, as it did not amplify any DNA products from the other species of human malaria parasites. We also mixed wild-type and mutant-type parasite DNAs in various proportions to determine how pyrosequencing, restriction fragment length polymorphism (RFLP), and direct conventional sequencing (for dhfr) compared with each other in detecting different SNPs in the mixture. In general, pyrosequencing and RFLP showed comparable sensitivities in detecting most of the SNPs in dhfr except for the 164L mutation, which required at least twice the amount of DNA for pyroseqencing as for RFLP. For detecting SNPs in dhps, pyrosequencing was slightly more sensitive than RFLP and direct sequencing. Overall, pyrosequencing was faster and less expensive than either RFLP or direct sequencing. Thus, pyrosequencing is a practical alternative method that can be used in a high-throughput format for molecular surveillance of antimalarial-drug resistance.

Animals↗
PubMed2004

Silver (I) cation specifically stabilizes heteroduplex with C:C mismatch base pair: toward the efficient detection of single nucleotide polymorphism (2).

We examined the effect of silver (I) cation on the thermal stability of heteroduplex and homoduplex. Addition of silver (I) cation increased the melting temperature of heteroduplex containing C:C mismatch base pair by about 3-4 degrees C. The thermal stability of homoduplex and heteroduplexes containing other kinds of mismatch base pairs was not significantly changed by the addition of silver (I) cation. We conclude that silver (I) cation specifically stabilizes heteroduplex containing C:C mismatch base pair. Our results certainly support the idea that the addition of silver (I) cation to C:C mismatch base pair in heteroduplex could be a convenient strategy for heteroduplex analysis and may eventually lead to progress in single nucleotide polymorphism genotyping.

Base Pair Mismatch↗
PubMed2005

Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3.

Although the bases for both the sporadic and inherited forms of Ménière's disease (MD) remain undefined, it is likely to be multifactorial, one of the factors being a genetic predisposition. Recently, genetic association studies on complex diseases have become very popular and most of them are case-control studies using single nucleotide polymorphisms (SNPs) as markers. Mutations/polymorphisms in KCNE potassium channel genes might play a causative role in MD, because KCNE potassium channels have been suggested to be present and active in transmembrane ion and water transports in the inner ear. In the present study, to identify MD susceptibility genes, we have conducted a genetic association study with optimized sampling, optimized phenotyping/genotyping, and a selection of KCNE genes as the candidate genes. The SNPs analyses identified 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene in 63 definite MD cases as well as 205 and 237 non-MD control subjects. For both KCNE1 and KCNE3 genes, a significant difference in frequency of each SNP was confirmed between MD cases and non-MD control subjects. The result indicates that 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene could determine an increased susceptibility to develop MD.

Adult↗
PubMed2004

Single nucleotide polymorphisms in protein tyrosine phosphatase 1beta (PTPN1) are associated with essential hypertension and obesity.

Protein tyrosine phosphatase 1beta (PTP-1beta) is involved in the regulation of several important physiological pathways. It regulates both insulin and leptin signaling, and interacts with the epidermal- and platelet-derived growth factor receptors. The gene is located on human chromosome 20q13, and several rare single nucleotide polymorphisms (SNPs) have been shown to be associated with insulin resistance and diabetes in different populations. As part of our ongoing investigations into the genetic basis of hypertension, we examined common sequence variants in the gene for association with hypertension, obesity and altered lipid profile in two populations of Japanese and Chinese descent. We re-sequenced all exons, selected intronic sequences and the promoter region in 24 individuals from our cohort. Fourteen SNPs were discovered, and six of these spanning 78 kb were genotyped in 1553 individuals from 672 families. All six SNPs were in linkage disequilibrium, and we found strong association of common risk haplotypes with hypertension in Chinese and Japanese (P<0.0001). In addition, individual SNPs showed association to total plasma cholesterol, LDL-cholesterol and VLDL-cholesterol levels, as well as obesity measures (body mass index). This analysis supports that PTP-1beta affects plasma lipid levels, and may lead to obesity and hypertension in Japanese and Chinese. Given similar associations found in other populations to insulin resistance and diabetes, this gene may play a crucial role in the development of the characteristic metabolic changes seen in patients with the metabolic syndrome.

Adult↗