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 1,027 records · Page 57Linked to original sources
PubMed2006

Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder.

Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers on chromosome 12, D12S86 and D12S378, was the most probable genomic region to contain a susceptibility gene for affective disorders. Association studies with microsatellite markers using a case/control sample from the same population (n = 427) revealed significant allelic associations between the bipolar phenotype and marker NBG6. Since this marker is located in intron 9 of the P2RX7 gene, we analyzed the surrounding genomic region for the presence of polymorphisms in regulatory, coding and intron/exon junction sequences. Twenty four (24) SNPs were genotyped in a case/control sample and 12 SNPs in all pedigrees used for linkage analysis. Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2 genes. The strongest association was observed in bipolar families at the non-synonymous SNP P2RX7-E13A (rs2230912, P-value = 0.000708), which results from an over-transmission of the mutant G-allele to affected offspring. This Gln460Arg polymorphism occurs at an amino acid that is conserved between humans and rodents and is located in the C-terminal domain of the P2X7 receptor, known to be essential for normal P2RX7 function.

Alleles↗
PubMed2006

Gene-associated single nucleotide polymorphism discovery in perennial ryegrass (Lolium perenne L.).

Molecular genetic marker development in perennial ryegrass has largely been dependent on anonymous sequence variation. The availability of a large-scale EST resource permits the development of functionally-associated genetic markers based on SNP variation in candidate genes. Genic SNP loci and associated haplotypes are suitable for implementation in molecular breeding of outbreeding forage species. Strategies for in vitro SNP discovery through amplicon cloning and sequencing have been designed and implemented. Putative SNPs were identified within and between the parents of the F(1)(NA(6) x AU(6)) genetic mapping family and were validated among progeny individuals. Proof-of-concept for the process was obtained using the drought tolerance-associated LpASRa2 gene. SNP haplotype structures were determined and correlated with predicted amino acid changes. Gene-length LD was evaluated across diverse germplasm collections. A survey of SNP variation across 100 candidate genes revealed a high frequency of SNP incidence (c. 1 per 54 bp), with similar proportions in exons and introns. A proportion (c. 50%) of the validated genic SNPs were assigned to the F(1)(NA(6) x AU(6)) genetic map, showing high levels of coincidence with previously mapped RFLP loci. The perennial ryegrass SNP resource will enable genetic map integration, detailed LD studies and selection of superior allele content during varietal development.

Breeding↗
PubMed2004

Fitness of Toxoplasma gondii is not related to DHFR single-nucleotide polymorphism during congenital toxoplasmosis.

Factors that regulate the pathogenesis of Toxoplasma gondii in humans are poorly understood. When acquired during pregnancy, toxoplasmosis can be disastrous, leading to fetal loss or conversely to subclinical disease. In congenitally infected infants, evolution is highly unpredictable. Genotype based virulence patterns have been described in mice, but in humans this classification does not correlate with the gravity of the disease. Mutations on DHFR-TS loci have recently been reported to confer T. gondii fitness cost. In this study, we investigated the relationship between the virulence of the parasite, as measured by clinical outcome in the fetus or newborn, fitness, as measured by parasitic load in amniotic fluid, and allelic polymorphism in DHFR. Six cases of severe congenital toxoplasmosis and 23 cases of mild congenital infections were included in the study. Quantitative PCR was performed to evaluate total T. gondii DNA load in amniotic fluid and detection of mutations was carried out with a LightCycler using hybridisation probes. Parasitic load was significantly higher in severe infections than in mild diseases. Among isolates from severe or non-severe cases of congenital toxoplasmosis, no polymorphism could be detected at loci 36, 83 or 245 of the DHFR gene. The virulent RH strain presented the same melting temperature as the non-virulent PRU strain for codons 36, 83 and 245. Only mutated clones, M2M3 and M2M4 with allelic replacement at these positions, displayed different profiles allowing a clear distinction between wild and mutant types. We concluded that the DHFR gene mutations we investigated do not regulate T. gondii fitness in humans.

Animals↗
PubMed2002

Single nucleotide polymorphism genotyping by on-line liquid chromatography-mass spectrometry in forensic science of the Y-chromosomal locus M9.

A method is described for genotyping alleles of the Y-chromosomal locus M9, incorporating DNA extraction, amplification by polymerase chain reaction (PCR), sample purification by ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC), and allele identification by on-line hyphenation to electrospray ionization mass spectrometry (ESI-MS). The alleles G and C were differentiated in 114 base pair amplicons on the basis of intact molecular mass measurements with a mass accuracy between 0.007 and 0.017%. The accuracy of mass determination was significantly reduced to less than 0.0036% upon amplification of a short, 61 bp fragment. The application of steep gradients of acetonitrile in 25 mM butyldimethylammonium bicarbonate not only enabled the efficient separation of non-target components from the PCR product in a monolithic, poly-(styrene-divinylbenzene)-based capillary column, but also allowed the high-throughput analysis of the PCR products with cycle times of 2 min. The new method was compared to a conventional restriction fragment length polymorphism assay with capillary gel electrophoretic analysis. In a blind study, 90 samples of unrelated individuals were genotyped. The high accuracy (<0.004%) and small relative standard deviation (<0.007%, n=20) of mass measurements, which enables even the differentiation of A and T alleles with a mass difference of 9 mass units, make IP-RP-HPLC-ESI-MS a potent tool for the routine characterization of SNPs in forensic science.

Base Sequence↗
PubMed2004

A functional single nucleotide polymorphism in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease.

In meningococcal sepsis, disseminated intravascular coagulation with deposition of fibrin and formation of microthrombi occurs in various organs and enhanced inhibition of fibrinolysis is associated with adverse outcome. Recently, TAFI (thrombin-activatable fibrinolysis inhibitor) was identified as a link between coagulation and fibrinolysis, as TAFI can be activated by thrombin and once activated potently attenuates fibrinolysis. On the basis of this one would predict that DNA polymorphisms that increase TAFI activity would deteriorate the outcome in meningococcal sepsis. Therefore, we studied the prevalence of the Thr325Ile dimorphism in the TAFI gene, which is associated with increased TAFIa stability and activity in 50 patients who survived meningococcal disease, in 176 first-degree relatives of a consecutive patient series with meningococcal disease and 212 controls from the same geographic region. The TAFI 325 Ile/Ile genotype was slightly more common among parents of patients with meningococcal disease than in controls (11% vs. 7.1%, P= 0.24). This difference was pronounced among the subgroup of parents of non-surviving patients (19.2%, P= 0.03). Patients whose parents were carriers of the TAFI 325 Ile/Ile genotype had a 1.6-fold (95% CI 0.7-3.7) higher risk to contract meningococcal disease and a 3.1-fold (95% CI 1.0-9.5) increased risk to die from the infection compared with all other genotypes. Survivors had a genotype frequency (4.0%) that was lower than in the general population. TAFI 325 variants affect the outcome of meningococcal disease.

Alleles↗
PubMed2006

Carotenoid biosynthesis structural genes in carrot (Daucus carota): isolation, sequence-characterization, single nucleotide polymorphism (SNP) markers and genome mapping.

Carotenoid pigments are important components of the human diet and carrots are the main dietary sources of the vitamin A precursors alpha- and beta-carotene. Carotenoids play essential biological roles in plants and the genes coding for the carotenoid pathway enzymes are evolutionarily conserved, but little information exists about these genes for carrot. In this study, we utilized published carrot sequences as well as heterologous PCR approaches with primers derived from sequence information of other plant species to isolate 24 putative genes coding for carotenoid biosynthesis enzymes in carrot. Twenty-two of these genes were placed on the carrot genetic linkage map developed from a cross between orange-rooted and white-rooted carrot. The carotenoid genes were distributed in eight of the nine linkage groups in the carrot genome recommending their use for merging maps. Two genes co-localized with a genomic region spanning one of the most significant quantitative trait loci (QTL) for carotenoid accumulation. Carotenoid biosynthesis cDNAs linked to root color mutations and to QTL for carotenoid accumulation may suggest a functional role for them as candidate genes. RACE PCR and reverse transcriptase PCR were used to amplify the full-length transcript for twenty expressed carotenoid biosynthesis genes and sequences were submitted to GenBank. The cloning and sequence information of these genes is useful for PCR-based expression studies and may point toward transgenic approaches to manipulate carotenoid content in carrot.

Base Sequence↗
PubMedDate not supplied

Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters.

The ATP-binding cassette (ABC) transporters constitute a large family of membrane proteins, which transport a variety of compounds through the membrane against a concentration gradient at the cost of ATP hydrolysis. Substrates of the ABC transporters include lipids, bile acids, xenobiotics, and peptides for antigen presentation. As they transport exogenous and endogenous compounds, they reduce the body load of potentially harmful substances. One by-product of such protective function is that they also eliminate various useful drugs from the body, causing drug resistance. This review is a brief summary of the structure, function, and expression of the important drug resistance-conferring members belonging to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. In the text, the transporter symbol that carries the subfamily name (such as ABCB1, ABCC1, etc.) is used interchangeably with the corresponding original names, such as MDR1P-glycoprotein, MRP1, etc., respectively. Both nomenclatures are maintained in the text because both are still used in the transporter literature. This helps readers relate various names that they encounter in the literature. It now appears that P-glycoprotein, MRP1, MRP2, and BCRP can explain the phenomenon of multidrug resistance in all cell lines analyzed thus far. Also discussed are the gene structure, regulation of expression, and various polymorphisms in these genes. Because genetic polymorphism is thought to underlie interindividual differences, including their response to drugs and other xenobiotics, the importance of polymorphism in these genes is also discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. RESULTS: The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]). CONCLUSION: These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.

Adult↗
PubMed2005

Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density.

The 12/15-lipoxygenase gene Alox15 has been identified as a susceptibility gene for bone mineral density (BMD) in mice through combined genetic and genomic analyses. Here we studied the association between bone mineral density and an ALOX15 gene single nucleotide polymorphism to assess the potential involvement of the human ALOX15 gene in postmenopausal osteoporosis. Specifically, we examined the association between a single nucleotide polymorphism at -5299G/A in the ALOX15 5'-flanking region with BMD in 319 postmenopausal Japanese women (66.7 +/- 8.9 years, mean +/- SD). We found that subjects bearing at least one variant A allele (GA + AA; n = 273) had significantly lower Z scores for lumbar spine and total body bone mineral density than did subjects with no A allele (GG; n = 46) (lumbar spine, -0.25 +/- 1.34 versus 0.48 +/- 1.70; P = 0.0014; total body, 0.25 +/- 1.01 vs 0.62 +/- 1.11; P = 0.048). These findings suggest that the ALOX15 gene is one of the genetic determinants of BMD in postmenopausal women. Accordingly, this polymorphism could be useful as a genetic marker for predicting the risk of osteoporosis.

Aged↗
PubMed2000

A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling.

Large scale sequencing of the human mu-opioid receptor (hMOR) gene has revealed polymorphic mutations that occur within the coding region. We have investigated whether the mutations N40D in the extracellular N-terminal region, N152D in the third transmembrane domain, and R265H and S268P in the third intracellular loop alter functional properties of the receptor expressed in mammalian cells. The N152D receptor was produced at low densities. Binding affinities of structurally diverse opioids (morphine, diprenorphine, DAMGO and CTOP) and the main endogenous opioid peptides (beta-endorphin, [Met]enkephalin, and dynorphin A) were not markedly changed in mutant receptors (<3-fold). Receptor signaling was strongly impaired in the S268P mutant, with a reduction of efficacy and potency of several agonists (DAMGO, beta-endorphin, and morphine) in two distinct functional assays. Signaling at N40D and R265H mutants was highly similar to wild type, and none of the mutations induced detectable constitutive activity. DAMGO-induced down-regulation of receptor-binding sites, following 20 h of treatment, was identical in wild-type and mutant receptors. Our data show that natural sequence variations in hMOR gene have little influence on ligand binding or receptor down-regulation but could otherwise modify receptor density and signaling. Importantly, the S268P mutation represents a loss-of-function mutation for the human mu-opioid receptor, which may have an incidence on opioid-regulated behaviors or drug addiction in vivo.

Analgesics, Opioid↗
PubMed2006

Role of single nucleotide polymorphisms of cytokine genes in spontaneous preterm delivery.

Intra-amniotic infections are implicated in spontaneous preterm delivery (PTD). Certain genetic polymorphisms are associated with increased production of proinflammatory and/or decreased production of anti-inflammatory cytokines, thereby possibly promoting PTD. We determined the relationship between maternal and fetal cytokine gene polymorphisms with occurrence and severity of spontaneous PTD (PTD after spontaneous-onset preterm labor and/or preterm prelabor rupture of membranes) and their association with intrauterine inflammation and infection. DNA from buccal brushings of 80 preterm (gestation < 35 weeks) and 80 matched term mother-infant pairs was assayed for tumor necrosis factor alpha (TNF-alpha [-308G/A]), interferon-gamma (IFN-gamma [+874A/T]), interleukin-6 (IL-6 [-174C/G]), interleukin-10 (IL-10 [-1082G/A, -819C/T, -592C/A]), and transforming growth factor beta1 (TGF-beta1 [T/Ccodon10,G/Ccodon25]) by using polymerase chain reaction (PCR) with sequence-specific primers. The presence of histologic chorioamnionitis was determined for PTDs. Conditioned on maternal IFN-gamma genotypes, fetal high IFN-gamma producing allele (IFN-gamma[+874T]) was associated with spontaneous PTD (odds ratio = 2.3 [1.2-4.4]). Among preterm deliveries, maternal low TGF-beta1 (TGF-beta1 [codon10C]) producing genotypes correlated negatively with gestation. Fetal TNF-alpha (-308G) was significantly associated with histologic chorioamnionitis. Underlying genitourinary infections and/or inflammation were significantly associated with maternal and fetal IL-6 (-174G), fetal TNF-alpha (-308GG), and fetal IL-10 (-1082A). We conclude that certain fetal and maternal cytokine gene polymorphisms may be associated with occurrence and/or severity of spontaneous PTD and with intrauterine inflammation and infection.

Adult↗
PubMed2001

Quantitative detection of single nucleotide polymorphisms for a pooled sample by a bioluminometric assay coupled with modified primer extension reactions (BAMPER).

A new method for SNP analysis based on the detection of pyrophosphate (PPi) is demonstrated, which is capable of detecting small allele frequency differences between two DNA pools for genetic association studies other than SNP typing. The method is based on specific primer extension reactions coupled with PPi detection. As the specificity of the primer-directed extension is not enough for quantitative SNP analysis, artificial mismatched bases are introduced into the 3'-terminal regions of the specific primers as a way of improving the switching characteristics of the primer extension reactions. The best position in the primer for such artificial mismatched bases is the third position from the primer 3'-terminus. Contamination with endogenous PPi, which produces a large background signal level in SNP analysis, was removed using PPase to degrade the PPi during the sample preparation process. It is possible to accurately and quantitatively analyze SNPs using a set of primers that correspond to the wild-type and mutant DNA segments. The termini of these primers are at the mutation positions. Various types of SNPs were successfully analyzed. It was possible to very accurately determine SNPs with frequencies as low 0.02. It is very reproducible and the allele frequency difference can be determined. It is accurate enough to detect meaningful genetic differences among pooled DNA samples. The method is sensitive enough to detect 14 amol ssM13 DNA. The proposed method seems very promising in terms of realizing a cost-effective, large-scale human genetic testing system.

Base Pair Mismatch↗
PubMed2001

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes.

Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context.

Asthma↗
PubMed2004

[Single nucleotide polymorphisms in XRCC1 and clinical response to platin-based chemotherapy in advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: DNA repair capacity correlated with sensitivity of cancer cells towards platin-based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin- or carboplatin-based chemotherapy of advanced non-small cell lung cancer (NSCLC). METHODS: Totally 105 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. RESULTS: The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1% vs. 20.3%;OR=2.97,95% CI=1.15-7.72;P< 0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5% vs. 21.2%;OR=2.65,95% CI=1.03-6.87;P< 0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7% which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0% to 23.1%, P< 0.001). CONCLUSION: Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin-based chemotherapy.

Adult↗
PubMed2005

Evaluation of linkage disequilibrium and its effect on non-parametric multipoint linkage analysis using two high density single-nucleotide polymorphism mapping panels.

Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of linkage disequilibrium (LD) between SNPs in a linkage analysis in the Collaborative Study on the Genetics of Alcoholism pedigree collection (143 pedigrees; 1,614 individuals). The average r2 between adjacent markers across the genetic map was 0.099 +/- 0.003 in the Illumina III panel and 0.17 +/- 0.003 in the Affymetrix 10 k array. In order to determine the effect of LD between marker loci in a nonparametric multipoint linkage analysis, markers in strong LD with another marker (r2 > 0.40) were removed (n = 471 loci in the Illumina panel; n = 1,804 loci in the Affymetrix panel) and the linkage analysis results were compared to the results using the entire marker sets. In all analyses using the ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were detected (peak markers p < 0.01), and the Illumina panel detected an additional region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3 chromosomes (peak markers p < 0.01). These results suggest that in this pedigree set, LD between loci with spacing similar to the SNP panels tested may not significantly affect the overall detection of linkage regions in a genome scan. Moreover, since the data quality and information content are greatly improved in the SNP panels over STR genotyping methods, new linkage regions may be identified due to higher information content and data quality in a dense SNP linkage panel.

Alcoholism↗
PubMed2004

The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3.

Insulin resistance is a major cause of type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, antagonizes insulin. Transgenic mice that overexpress the resistin gene (Retn) in adipose tissue are insulin-resistant, whereas Retn (-/-) mice show lower fasting blood glucose, suggesting that the altered Retn promoter function could cause diabetes. To determine the role of RETN in human T2DM, we analyzed polymorphisms in its 5' flanking region. We found that the -420G/G genotype was associated with T2DM (397 cases and 406 controls) (P=.008; adjusted odds ratio = 1.97 [by logistic regression analysis]) and could accelerate the onset of disease by 4.9 years (P=.006 [by multiple regression analysis]). Meta-analysis of 1,888 cases and 1,648 controls confirmed this association (P=.013). Linkage disequilibrium analysis revealed that the -420G/G genotype itself was a primary variant determining T2DM susceptibility. Functionally, Sp1 and Sp3 transcription factors bound specifically to the susceptible DNA element that included -420G. Overexpression of Sp1 or Sp3 enhanced RETN promoter activity with -420G in Drosophila Schneider line 2 cells that lacked endogenous Sp family members. Consistent with these findings, fasting serum resistin levels were higher in subjects with T2DM who carried the -420G/G genotype. Therefore, the specific recognition of -420G by Sp1/3 increases RETN promoter activity, leading to enhanced serum resistin levels, thereby inducing human T2DM.

Aged↗
PubMed2005

Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region.

Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers D12S86 and D12S378 on chromosome 12 was the most probable genomic region to contain a susceptibility gene for affective disorders. Here we present a more detailed genetic analysis of a 7.7 Mb genomic region located on 12q24.31. This region was saturated with 20 microsatellite markers to refine the candidate region and linkage analysis performed in 41 families from the Saguenay-Lac-St-Jean (SLSJ) region of Quebec. The results of two point parametric analysis using MFLINK supported the presence of a susceptibility locus on chromosome 12q24.31. Association studies with microsatellite markers using a case/control sample from the same population (n = 401) and analyzed with CLUMP revealed significant allelic associations between the bipolar phenotype and markers NBG6 (P = 0.008) and NBG12 (P < 10(-3)). According to these results, we investigated candidate genes in the NBG12 area. We analyzed 32 genes for the presence of polymorphisms in coding sequences and intron/exon junctions and genotyped 22 non-synonymous SNPs in the SLSJ case/control sample. Two uncommon polymorphisms (minor allele frequency < or = 0.03) found in KIAA1595 and FLJ22471 genes, gave P-values below 0.05 with the T1 statistic. Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene. These results do not give strong support for a role in the susceptibility to bipolar disorder of any of these genes analyzed. However, the significance of rare polymorphisms should be explored by further analyses.

Alleles↗
PubMed2001

Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy and a major cause of irreversible blindness, with elevation of intraocular pressure (IOP) being a primary risk factor. The trabecular meshwork-inducible glucocorticoid response (TIGR)/MYOCILIN (MYOC) gene coding region is mutated in 3-4% of POAG patients. Here, in a retrospective study of 142 POAG patients, we evaluated the influence on glaucoma phenotype of a novel biallelic polymorphism (-1000C/G) located in the upstream region of the MYOC gene. Allele frequencies were similar among patients and controls. However, the G allele (frequency 17.6%), also designated as MYOC.mt1, was associated with an increased IOP (+4.9 mmHg, p=0.0004) and a more damaged visual field (p=0.02). Both effects were predominant in females. Moreover, whereas IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range between diagnosis and inclusion in the study (p=3 x 10(-5) in both males and females), reflecting successful therapy, it decreased less noticeably in MYOC.mt1+ male patients (p=0.005) and not at all in MYOC.mt1+ female patients. MYOC.mt1 appears therefore to be an indicator of poor IOP control and greater visual field damage in diagnosed POAG patients, potentially due to a lack of response to therapeutic intervention. Its typing might help in the selection of treatment paradigms for the management of POAG patients.

Alleles↗