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At least 199 records · Page 11Linked to original sources
PubMed2006

Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma.

BACKGROUND: PTGDR gene has been identified as an asthma-susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study -549T>C, -441C>T and -197T>C PTGDR promoter polymorphisms in a Spanish population. METHODS: In this study, 197 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the American Thoracic Society (ATS) criteria and classified following the Global Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all patients. The polymorphisms were analyzed by direct sequencing. RESULTS: -197T>C polymorphism was significantly associated with asthma [Fisher's P-value = 0.007, Monte Carlo P-value (10(4) simulations) = 0.004]. Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of asthma (OR, 3.06; 95% CI, 1.28-7.32; P-value = 0.012). CCT CCC diplotype was associated with asthma (P-value < 0.0001; OR, 1.15; 95% CI, 1.07-1.23), specifically with allergic asthma (P-value < 0.0001). CCT CCC diplotype is unambiguous. All individuals carrying this diplotype had asthma. CONCLUSION: We identified a specific promoter variant of PTGDR that could be associated with asthma. This diplotype is a combination of the two highest transcriptional efficiency haplotypes, recently described. Our in vivo results would support for the first time what was demonstrated in vitro about high-transcriptional efficiency PTGDR haplotypes in asthma.

Adult↗
PubMed1996

Genetic variants of the human obesity (OB) gene: association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene.

To examine the possible role of genetic variants of the OB gene in obesity we examined alleles of a dinucleotide repeat polymorphism, D7S1875, close to the gene, in a group of adult, non-Hispanic Caucasians. There was a significant correlation with body mass index (BMI) at age 26-30 years for males and females combined (P = 0.04) and females only (P = 0.028). Because of the frequent association between obesity and psychiatric symptoms all subjects were screened with the Symptom List 90 (SCL-90). There was a significant increase in scores for anxiety (P = 0.0005), depression (P = 0.003), and other behaviors for subjects homozygous for the OB1875 < 208-bp alleles. Analysis of covariance indicated that this was directly related to the OB alleles and not secondary to the presence of obesity. There was a significant association between the BMI at ages 16 to 40 and homozygosity for the OB1875 < 208-bp alleles and/or the presence of the DRD2 Taq A1 allele for males and females combined (P = 0.002 to 0.005), and for females alone (P = 0.0017 to 0.0005). For females alone these two genes accounted for up to 22.8% of the variance of the BMI. These results are consistent with the polygenic inheritance of obesity, the greater involvement of genetic factors in women and younger individuals, and suggest that variants of the OB gene are causally involved not only in human obesity but its associated behavioral disorders.

Adult↗
PubMed1990

Two of the three genetic variants of goat alpha s1-casein which are synthesized at a reduced level have an internal deletion possibly due to altered RNA splicing.

This paper describes the elucidation of the primary structure of the three genetic variants of goat alpha s1-casein, alpha s1-Cn D, E and F, which have been found to be associated with reduced amounts of alpha s1-casein in milk. Variant E has the same electrophoretic mobility as variant B, but differs from the latter by the substitutions of Arg for Lys and of Thr for Ala at positions 100 and 195. A genetically controlled event which does not affect the amino acid sequence of this variant might be responsible for its lower rate of synthesis compared to that of alpha s1-casein B. The deletion of 11 amino acids at positions 59-69 and of 37 amino acids at positions 59-95 in variant B leads to variants D and F. In both cases the deletions, which start at the same position of the polypeptide chain, include the major phosphorylation site of the protein. On the basis of sequence data for casein genes and cDNAs, it was concluded that the deletions occurring in the D and F variants are due to the exclusion of one and several exons, respectively. The observed deletions in the proteins could thus be the consequence of splice site mutations which would induce altered RNA processing and hence reduce the rate of synthesis of the casein.

Amino Acid Sequence↗
PubMed1997

Structural characterization of four genetic variants of human serum albumin associated with alloalbuminemia in Italy.

A long-term electrophoretic survey on plasma proteins, which was carried out in several clinical laboratories in Italy, identified 28 different genetic variants of human serum albumin and four cases of analbuminemia. We have previously characterized 16 point mutations, 3 C-terminal mutants, and the genetic defects in two analbuminemic subjects. Here, we report the molecular defects of four alloalbumins that have been characterized by protein structural analysis. Of these, three represent new single-point mutations: albumins Tregasio, Val122-->Glu, Bergamo, Asp314-->Gly, and Maddaloni, Val533-->Met. The fourth, albumin Besana Brianza, has the same Asp494-->Asn mutation that introduces a glycosylation site which has been previously reported in a variant from New Zealand, albumin Casebrook. However, in contrast to albumin Casebrook, albumin Besana Brianza is only partially glycosylated and the oligosaccharide is heterogeneous, consisting of a biantennary complex type N-glycan with either two or one sialic acid residue(s) on the antennae. Both albumin Maddaloni and Besana Brianza represent mutations at hypermutable CpG dinucleotide sites; albumin Maddaloni is a mutant that does not involve a charged amino acid.

Amino Acid Sequence↗
PubMed2003

Mass mapping analysis as a tool for the identification of genetic variants of bovine beta-casein.

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometric analysis of the tryptic digest of beta-casein A2 and beta-casein B was performed before and after the separation of the peptides by LC. The overlapping of the chromatograms showed that all peaks were present in both samples, except for one only found in the tryptic digest of the A2 variant and two in the B variant. Experimental masses could be assigned to those peptides produced by tryptic digest of beta-casein variant. This peptide mapping strategy and current methodological improvements represent a promising tool for the identification of milk genetic variants with the difference of an amino acid substitution.

Amino Acid Sequence↗
PubMed1996

Relations between aggregative, viscoelastic and molecular properties in gluten from genetic variants of bread wheat.

Glutens differing in their low- and high-molecular-weight glutenin subunits (LMW-GS and HMW-GS) were extracted from genetic variants of bread wheat. Their composition was analysed by electrophoresis, the glutenin size distribution was determined by size-exclusion chromatography. Rheological measurements in the dynamic regime and electron spin resonance spin-labelling experiments gave data on the viscoelasticity and the protein flexibility of the glutens, respectively. In glutens differing in their HMW-GS, a relation is observed between the composition, aggregative properties, segmental flexibility and viscoelastic behaviour. This is not found in glutens with different LMW-GS. However, the proportion of rigid polypeptide segment is related to the height of the elastic plateau in all cases. The organisation of the protein network in gluten is discussed in reference to this data.

Electron Spin Resonance Spectroscopy↗
PubMed1997

Identification of genetic variants of hepatitis A virus.

Although detection of hepatitis A virus (HAV) has been greatly aided by the development of polymerase chain reaction (PCR) technology, identification of genetic variants requires sequencing PCR products, which necessarily limits the length of the HAV genome (typically 2%) that can be analyzed. From a regulatory standpoint, identification of the specific strain detected by PCR is a prerequisite not only to overrule contamination of test samples in the diagnostic laboratory, but also to possibly locate the origin of the virus detected by PCR. We explored alternatives to sequencing PCR products to achieve these goals. The findings indicate that restriction fragment length polymorphism (RFLP) analysis of PCR products from two noncontiguous regions of the HAV genome encompassing 765 nucleotides (approximately 10% of the genome) by the restriction endonucleases HinfI and AluI, which cut frequently within the HAV genome, can distinguish the common tissue culture adapted strains of HAV from stool isolates. The resolution can be greatly enhanced by combining single strand conformation polymorphism (SSCP) analysis with restriction enzyme digestion, when most of the seventeen strains analyzed could be identified.

DNA, Viral↗
PubMed2006

Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study.

CONTEXT: Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD). OBJECTIVE: The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein lipase genotypes on triglycerides, HDL, and IHD. DESIGN: The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively. SETTING: The study was performed in the Danish general population (the Copenhagen City Heart Study). PARTICIPANTS: IHD was angina pectoris or myocardial infarction. MAIN OUTCOME MEASURES: Triglycerides, HDL, and IHD were the main outcome measures. RESULTS: Cross-sectionally, triglycerides varied by genotype with 1.27 mmol/liter in women and 1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD of 1.6 [95% confidence interval (CI), 1.2-2.3]; 291Ser and 447Ter did not change IHD risk. In the case-control study, combining the cohorts of IHD patients, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had an odds ratio for IHD of 1.5 (CI, 1.2-2.1). 291Ser and 447Ter did not change IHD risk. Stratified for apolipoprotein E genotype, the odds ratios for IHD in 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers were 2.6 (CI, 1.2-5.5) among epsilon32 individuals and 2.4 (CI, 1.4-4.1) among epsilon43 individuals. CONCLUSIONS: Genetic variation in lipoprotein lipase is associated with differences in plasma triglycerides greater than 1 mmol/liter and differences in HDL cholesterol greater than 0.5 mmol/liter. A 1.6-fold risk of IHD in 9Asn (with -93G) heterozygotes and homozygotes combined is influenced by apolipoprotein E genotype.

Adult↗
PubMed2003

Glycosylation study of the major genetic variants of human alpha1-acid glycoprotein and of their pharmacokinetics in the rat.

Human alpha1-acid glycoprotein (AAG) is a mixture of at least two genetic variants, the A variant and the F1 and/or S variant or variants, which are encoded by two different genes. AAG is also an extensively glycosylated protein which possesses five N-linked glycans exhibiting substantial heterogeneity in their structures. The first objective of this study was to investigate the glycosylation of the two major gene products of AAG, i.e. the A variant and a mixture of the F1 and S variants (F1*S). To this end, we combined a chromatographic method for the fractionation of the AAG variants with a lectin-binding assay to characterise the glycosylation of purified glycoproteins. Secondly, because the oligosaccharides can influence the disposition of AAG, a kinetic study of the AAG variants was carried out in the rat. After intravenous administration of whole human AAG, the separation and quantification of the AAG variants in plasma was performed by application of specific methods by isoelectric focusing and immunonephelometry. The binding studies carried out on a panel of lectins showed significant differences in the lectin-binding characteristics of the separated F1*S and A variants, accounting for differences in the degree of branching of their glycan chains and substitution with sialic acid and fucose. The plasma concentration-time profiles of the F1*S and A variants were biphasic, and only small differences were observed between the variants for their initial and terminal half-lives, clearance and distribution volume. This indicates that the structural differences between the two AAG gene products do not affect their pharmacokinetics in the rat. Specific drug transport roles have been previously demonstrated for the F1*S and A variants, calling for further investigations into their effects on the disposition of drugs they bind in plasma. The present study shows that such investigations are possible without being complicated by kinetic differences between these variants.

Animals↗
PubMed1998

Genetic variants of the human obesity (OB) gene in subjects with and without Prader-Willi syndrome: comparison with body mass index and weight.

We investigated whether an association exists between genetic variants of the human obesity (OB or leptin) gene and body mass index (BMI) or weight in subjects with Prader Willi syndrome (PWS) and in age- and gender-matched lean and obese subjects without PWS. The study included 51 subjects with PWS (mean age = 17.7 +/- 9.5 years, BMI = 29.7 +/- 8.3 kg/m2); 50 non-PWS obese subjects (mean age = 18.2 +/- 10.8 years, BMI = 33.3 +/- 9.5 kg/m2); and 53 non-PWS lean subjects (mean age = 17.8 +/- 9.5 years, BMI = 19.5 +/- 2.9 kg/m2). Allele sizes were determined via standard polymerase chain reaction of the D7S1875 locus, a dinucleotide repeat polymorphism close to the OB gene and classified as trichotomous (homozygous < 208 bp, heterozygous < 208/ > or = 208 bp, homozygous > or = 208 bp) or dichotomous (homozygous < 208 bp or not). Non-PWS males showed a marked decrease in weight with larger alleles while females did not (interaction effect, p < 0.05). Comparable effects were not observed among the PWS subjects. Associations between BMI and genotype were statistically significant (r = 0.22, one-tailed p < 0.05) and comparable to previous research among the non-PWS subjects < 18 years, but not the adults (r = 0.05, one-tailed p = 0.38). Correlations were not statistically significant among either the adult or non-adult PWS subjects.

Adult↗
PubMed1986

Identification of an antigenic and genetic variant of dengue-4 virus from the Caribbean.

Twenty-one dengue (DEN) viruses isolated from the Caribbean (Dominica and Jamaica) during the 1981-1982 epidemic year were distinct serological and genetic variants of DEN-4 virus. These isolates were clearly identified as DEN-4 viruses using type-specific monoclonal antibodies in indirect immunofluorescence assays. However, they either were not neutralized, or were neutralized poorly using hyperimmune mouse ascitic fluids (HMAF) or rhesus monkey serum directed against the H-241 prototype strain of DEN-4 virus isolated in the Philippines in 1956. HMAF prepared against a representative Caribbean isolate, however, neutralized with similar effectiveness the homologous virus, the H-241 prototype strain, and virus strains isolated from the Pacific and Southeast Asian areas from 1973 to 1984. The Caribbean isolate exhibited no more than 30% and 16% oligonucleotide spot homology with the H-241 and Bangkok viruses, respectively, by RNA fingerprint analysis, while demonstrating 82% and 89% homology with the Gilbert and Niue Island isolates, respectively. The isolation of dengue viruses which are serologically and genetically distinct from the prototype virus emphasizes the need for continued dengue virus surveillance. The recognition of unique dengue isolates should allow the selection of reference strains and vaccine candidate strains which will induce antibodies that are equally effective in neutralizing viruses from all geographic areas.

Aedes↗
PubMed1988

Allergenic properties of the genetic variants A and B of bovine beta-lactoglobulin.

The principal allergen in cow's milk is beta-lactoglobulin (beta-Lg) which is normally found as equal mixtures of the A and B genetic variants in pooled milk. The A and B variants were purified in large amounts and fed to guinea pigs. After 15 days, circulating immunoglobulins IgG1 and IgG2 to the milk proteins were detected, with a somewhat higher response to beta-Lg A than B. Sensitised guinea pigs succumbed to anaphylactic shock when challenged intracardially with either variant. The higher response is likely to be due to amino acid residues found only in the A variant, lying in surface regions of the molecule.

Allergens↗
PubMed2005

Congenital heart defects and genetic variants in the methylenetetrahydroflate reductase gene.

BACKGROUND: Most non-syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C-->T and 1298A-->C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene decrease enzyme activity. OBJECTIVE: To examine the relation between CHD and maternal and fetal MTHFR polymorphisms. METHODS: 375 nuclear families were studied. The transmission/disequilibrium test was used to test for transmission distortion in complete triads. A log-linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out. RESULTS: The 1298C allele was transmitted less often than expected (p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C-1298C haplotype was also transmitted less often than expected (p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70). CONCLUSIONS: The apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.

Alleles↗
PubMed2003

Two genetic variants of the crustacean hyperglycemic hormone (CHH) from the Australian crayfish, Cherax destructor: detection of chiral isoforms due to posttranslational modification.

From sinus glands of the Australian crayfish Cherax destructor, two genetic variants of the crustacean hyperglycemic hormone (CHH) were isolated by HPLC and fully characterized by mass spectrometry and Edman sequencing. Both CHH A (8350.38 Da) and CHH B (8370.34 Da) consist of 72 amino acid residues, with pyroGlu as N-terminus and an amidated (Val-NH2) C-terminus. They differ in 14 residues (81% identity). Both sequences are significantly different from those of the hitherto known three CHHs of Astacoidea species (Northern hemisphere crayfish), which among themselves are extremely conserved. This may reflect the long, separate evolution of the Astacoidea lineage and the Parastacoidea (Southern hemisphere crayfish) lineage, to which Cherax belongs. CHH A and CHH B genes are expressed at comparable levels, as indicated by the similar amounts of mature peptides in the sinus gland. In addition to each of the major peptides, which share the identical N-terminal tripeptide pyroGlu-Val-L-Phe, one chiral isoform containing pyroGlu-Val-D-Phe was identified. Compared to the main peptides, the amounts of the D-isoforms are lower, but significant, amounting to 30-40% of L-isoforms. These results demonstrate that two genes can give rise to a total of four different peptides in the secretory terminals of the sinus gland. All peptides gave a highly significant hyperglycemic in vivo response in C. destructor.

Amino Acid Sequence↗
PubMed2003

Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease.

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.

Analysis of Variance↗
PubMed2025

Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.

CONTEXT: The response to treatment with vitamin D varies between patients. OBJECTIVE: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation. DESIGN: Randomized placebo-controlled trial conducted between 2017 and 2019. SETTING: The trial was nested in an ongoing community-based cohort study, the Multi-Ethnic Study of Atherosclerosis. INTERVENTION: 2000 International Units of vitamin D3 or placebo daily for 16 weeks. PARTICIPANTS: The analytic sample included 427 participants assigned to vitamin D3 (mean age, 73 years; 54% females) and was 36% White, 33% Black, 18% Hispanic, and 14% Chinese. MAIN OUTCOME MEASURES: The biochemical response to vitamin D3 included changes in serum concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], PTH, and 25-hydroxyvitamin D3 [25(OH)D3]. RESULTS: In genome-wide analyses, single nucleotide polymorphisms in 8 regions of the genome had significant association (P < 5E-08) with 1 of the traits (2 with change in 1,25(OH)2D3, 1 with change in PTH, and 5 with change in 25(OH)D3). rs16867276 within an intergenic region on 2q31 was associated with change in serum 1,25(OH)2D3 (+8.37&#x2005;pg/mL difference per effect allele; P = 4.93E-08) and was the only locus that achieved genome-wide significance in transethnic meta-analysis. rs114044709 adjacent to FAM20A, which encodes a protein required for biomineralization, was associated with change in PTH among Black participants (+20.32&#x2005;pg/mL difference per effect allele; P = 1.34E-08). In candidate analyses, single nucleotide polymorphisms within SULT2A1 and CYP24A1 had significant association (P < .05&#xf7;36 = .0014) with the changes in 1,25(OH)2D3 and PTH, respectively. CONCLUSION: Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.

Humans↗
PubMed2006

APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians.

The cytosine deaminase APOBEC3G has been identified as a host factor that inhibits HIV-1 replication. We investigated whether genetic variants of APOBEC3G that could potentially affect the protein's expression or function were associated with the risk of infection in 122 Caucasians highly exposed to HIV-1. A novel C40693T variant was significantly associated with an increased risk of infection, suggesting that there might be a role for APOBEC3G in susceptibility to HIV-1 infection that warrants further investigation.

APOBEC-3G Deaminase↗