Association of genetic variants of oxidative stress responsive kinase 1 (OXSR1) with asthma exacerbations in non-smoking asthmatics

Background Asthma exacerbation threatens patient's life. Several genetic studies have been conducted to determine the risk factors for asthma exacerbation, but this information is still lacking. We aimed to determine whether genetic variants of Oxidative Stress Responsive Kinase 1 (OXSR1), a gene with functions of salt transport, immune response, and oxidative stress, are associated with exacerbation of asthma. Methods Clinical data were obtained from 1454 asthmatics and single nucleotide polymorphisms (SNPs) of OXSR1 were genotyped. Genetic associations with annual exacerbation rate were analyzed depending on smoking status. Results Eleven SNPs were selected using Asian data in the International HapMap database. The common allele of rs1384006 C > T of OXSR1 showed a significantly higher annual exacerbation rate than the rare allele in non-smoking asthmatics (CC vs. CT vs. TT: 0.43 ± 0.04 vs. 0.28 ± 0.03 vs. 0.31 ± 0.09, P = 0.004, Pcorr = 0.039). The frequent exacerbators had a significantly higher frequency of the common allele of rs1384006 C > T than did the infrequent exacerbators (74.4% vs. 55.2%, P = 0.004, Pcorr = 0.038). Conclusion The common allele of rs1384006 C > T of OXSR1 was associated with the asthma exacerbation rate and a higher risk of being a frequent exacerbator, indicating that non-smoking asthmatics who carry common alleles may be vulnerable to asthma exacerbations.

Matrix Metalloproteinase 2 Is Associated With Secondary Caries Independent From the Restorative Material

Certain patients, despite receiving proper treatment, still show higher failure rates of restorative dental treatments. The aim of this work was to test if MMP2 and MMP3 alleles are overrepresented in individuals with secondary caries. A total of 1,089 individuals from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project were selected for this study. From this total, 341 individuals were selected for having a record of secondary caries in any type of restoration and were matched with 748 individuals by sex, age, ethnicity, and restorative work in the same teeth that did not fail. Genomic DNA extracted from saliva was used to obtain genotypes in five markers of MMP2 and MMP3 using TaqMan chemistry and end-point analysis. Chi-square was used to test if differences in allele and genotype distributions were statistically different at an alpha of 0.05. The less common allele and homozygote genotype of MMP2 rs9923304 were less commonly found among individuals with secondary caries. The less common allele of MMP2 rs2287074 was also less frequent among individuals with secondary caries. These results provide statistical evidence for the role of MMP2 in failure of restorations due to secondary caries. We can conclude that MMP2 variation impacts the risk of having secondary caries, independent of the restorative material.

Association of Genetic Variants of Oxidative Stress Responsive Kinase 1 (OXSR1) with Asthma Exacerbations in Non-Smoking Asthmatics

Background: Asthma exacerbation threatens patient's life. Several genetic studies have been conducted to determine the risk factors for asthma exacerbation, but this information is still lacking. We aimed to determine whether genetic variants of Oxidative Stress Responsive Kinase 1(OXSR1), a gene with functions of salt transport, immune response, and oxidative stress, are associated with exacerbation of asthma.Methods: Clinical data were obtained from 1,454 asthmatics and single nucleotide polymorphisms (SNPs) of OXSR1 were genotyped. Genetic associations with annual exacerbation rate were analyzed depending on smoking status. Results: Eleven SNPs were selected using Asian data in the International HapMap database. The common allele of rs1384006 C>T of OXSR1 showed a significantly higher annual exacerbation rate than the rare allele in non-smoking asthmatics (CC vs. CT vs. TT: 0.43 ± 0.04 vs. 0.28 ± 0.03 vs. 0.31 ± 0.09, P=0.004, Pcorr=0.039). The frequent exacerbators had a significantly higher frequency of the common allele of rs1384006 C>T than did the infrequent exacerbators (74.4% vs. 55.2%, P=0.004, P corr=0.038). Conclusion: The common allele of rs1384006 C>T of OXSR1 was associated with the asthma exacerbation rate and a higher risk of being a frequent exacerbator, indicating that non-smoking asthmatics who carry common alleles may be vulnerable to asthma exacerbations.

Genetic characteristics of the Pechora type of Kholmogorsky cattle based on microsatellites and DNA markers

The Pechora zonal type (PH-1) was obtained by absorbing crossbreeding of local Northern komolog cattle with the Kholmogorsky breed. Currently, Kholmogorsky cattle are on the verge of extinction, which is due to the widespread metisation of domestic Holstein breeds. The paper presents the characteristics of the allelofond of the Kholmogorsky herd of the Pechora type (n=66) by 11 polymorphic loci of microsatellites. It was found that the polymorphism of tandem repeats in the Pechora type of Kholmogorsky cattle is observed in all 11 loci, the most polymorphic is the tgla53 locus (10 alleles). The most common allele SPS115 248 occurs with a frequency of 0.606. The average number of alleles for 11 loci was 6.2, and the number of effective alleles was 3.4. the obtained indicators were compared with the values published for Yakut [1], Holstein [2, 3] and Ayrshire cattle [4]. It was found that the Pechora type of Kholmogorsky breed has a higher number of effective alleles than Yakut cattle (by 1.0), and lower than other breeds (by 0.3...1.6). Analysis of F-statistics showed that on average, the deviation of the actual heterozygosity from the expected one is insignificant Fis=-0.004, while other breeds, excluding the sample of Holstein bulls, had a more significant excess of heterozygotes. The smallest genetic distance of the studied population was established with the Holstein breed (d=0.221 to cows and d=0.200 to bulls). A more detailed genetic analysis of individual loci showed that the frequency of occurrence of alleles BM2113 Pechora type is closer to the Yakut (r=0.935) and Ayrshire (r=0.875) than to the Holstein breed (r=316...357).

Accuracy of Imputation of Microsatellite Markers from a 50K SNP Chip in Spanish Assaf Sheep

Transitioning from traditional to new genotyping technologies requires the development of bridging methodologies to avoid extra genotyping costs. This study aims to identify the optimum number of single nucleotide polymorphisms (SNPs) necessary to accurately impute microsatellite markers to develop a low-density SNP chip for parentage verification in the Assaf sheep breed. The accuracy of microsatellite marker imputation was assessed with three metrics: genotype concordance (C), genotype dosage (length r2), and allelic dosage (allelic r2), for all imputation scenarios tested (0.5–10 Mb microsatellite flanking SNP windows). The imputation accuracy for the three metrics analyzed for all haplotype lengths tested was higher than 0.90 (C), 0.80 (length r2), and 0.75 (allelic r2), indicating strong genotype concordance. The window with 2 Mb length provides the best accuracy for the imputation procedure and the design of an affordable low-density SNP chip for parentage testing. We additionally evaluated imputation performance under two null models, naive (imputing the most common allele) and random (imputing by randomly selecting the allele), which in comparison showed weak genotype concordances (0.41 and 0.15, respectively). Therefore, we describe a precise methodology in the present article to impute multiallelic microsatellite genotypes from a low-density SNP chip in sheep and solve the problem of parentage verification when different genotyping platforms have been used across generations.

Association of Apolipoprotein E Polymorphisms with White Matter Lesions and Brain Atrophy

Objective Apolipoprotein E (ApoE) is mainly synthesized in the liver. So far, it is unknown the relationship among <i>APOE</i> gene polymorphisms and WML, brain atrophy. Therefore, the aim of the study was to assess the associations of <i>APOE</i> gene polymorphisms in patients with WML and brain atrophy.Methods A total of 58 patients with WML, 128 patients with brain atrophy, 112 patients with co-occurrence of WML and brain atrophy and 95 healthy elderly volunteers were recruited from Renmin Hospital of WuHan University.Results Allele <i>E3</i> was the most common allele. The alleles <i>E2</i> had significantly higher levels of ApoB and lower age in WML group. The alleles <i>E2</i> was associated with the lower level of ApoB, LDL-Ch, TCh, and sdLDL in co-occurrence group. The <i>E3</i>/<i>E3</i> genotype has higher level of sdLDL, but lower age and female frequency in WML. The <i>E3</i>/E4 genotype had higher level of TG, but lower age in WML. Gender, Age, <i>E2</i>, Hyperhomocysteinemia and UA were also significantly associated with disease progression.Conclusion This study found that clinical data, lipids and metabolic complications were closely related to ApoE genotypes and alleles, and also disease progression and type.

Consequences of PCA graphs, SNP codings, and PCA variants for elucidating population structure

SNP datasets are high-dimensional, often with thousands to millions of SNPs and hundreds to thousands of samples or individuals. Accordingly, PCA graphs are frequently used to provide a low-dimensional visualization in order to display and discover patterns in SNP data from humans, animals, plants, and microbes—especially to elucidate population structure. Given the popularity of PCA, one might expect that PCA is understood well and applied effectively. However, our literature survey of 125 representative articles that apply PCA to SNP data shows that three choices have usually been made poorly: PCA graph, SNP coding, and PCA variant. Our main three recommendations are simple and easily implemented: Use PCA biplots, SNP coding 1 for the rare allele and 0 for the common allele, and double-centered PCA (or AMMI1 if main effects are of interest). The ultimate benefit from informed and optimal choices of PCA graph, SNP coding, and PCA variant, is expected to be discovery of more biology, and thereby acceleration of medical, agricultural, and other vital applications.

A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

SummaryFibroblast Growth Factor 21 (FGF21) is a hormone that induces weight loss in model organisms. These findings have led to trials in humans of FGF21 analogues with some showing weight loss and lipid lowering effects. Recent genetic studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with body fat distribution, with less fat in the lower body, and higher blood pressure, than it is with BMI, where there is only nominal evidence of an effect. These human phenotypes of naturally occurring variation in the FGF21 gene will inform decisions about FGF21’s therapeutic potential.