Related Single Nucleotide Polymorphisms Research Articles

Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed toexamine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

An analysis of the relationship between ABCC8 and KCNJ11 gene polymorphisms and diabetic retinopathy in Turkish population

ABSTRACT Background Diabetic retinopathy (DR) occurs due to high blood glucose damage to the retina and leads to blindness if left untreated. KATP and related genes (KCNJ11 and ABCC8) play an important role in insulin secretion by glucose-stimulated pancreatic beta cells and the regulation of insulin secretion. KCNJ11 E23K (rs5219), ABCC8–3 C/T (rs1799854), Thr759Thr (rs1801261) and Arg1273Arg (rs1799859) are among the possible related single nucleotide polymorphisms (SNPs). The aim of this study is to find out how DR and these SNPs are associated with one another in the Turkish population. Materials and methods This study included 176 patients with type 2 diabetes mellitus without retinopathy (T2DM-rp), 177 DR patients, and 204 controls. Genomic DNA was extracted from whole blood, and genotypes were determined by the PCR-RFLP method. Results In the present study, a significant difference was not found between all the groups in terms of Arg1273Arg polymorphism located in the ABCC8 gene. The T allele and the TT genotype in the −3 C/T polymorphism in this gene may have a protective effect in the development of DR (p = 0.036 for the TT genotype; p = 0.034 for T allele) and PDR (p = 0.042 and 0.025 for the TT genotype). The AA genotype showed a significant increase in the DR group compared to T2DM-rp in the KCNJ11 E23K polymorphism (p = 0.046). Conclusions Consequently, the T allele and TT genotype in the −3 C/T polymorphism of the ABCC8 gene may have a protective marker on the development of DR and PDR, while the AA genotype in the E23K polymorphism of the KCNJ11 gene may be effective in the development of DR in the Turkish population.

Abstract WP254: Genetic Insights Into Snoring On Stroke

Background: Multiple risk factors of stroke have been identified in previous studies; however, the causal role of snoring in the onset of stroke is less investigated. To clarify the causal association of snoring on stroke and its subtypes, this study is performed. Methods: The single nucleotide polymorphisms in relation to snoring were retrieved from the UK biobank cohort with 408,317 participants. The data for stroke and its subtypes of European ancestry (67,162 cases and 453,702 controls) were obtained from the MEGASTROKE consortium. In single-variable Mendelian randomization (SVMR) and multivariable MR (MVMR) analyses, inverse variance weighting was used as the primary estimate, complemented with sensitivity analyses more robust to pleiotropy. Results: Genetically predicted snoring increased the risk of stroke (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.19-6.08, P = 0.016) and ischemic stroke (IS) (OR = 2.82, 95% CI = 1.23-6.44, P = 0.013), but not large artery stroke (LAS) (OR = 3.02, 95% CI = 0.31-29.44, P = 0.339), cardioembolic stroke (CES) (OR = 1.51, 95% CI = 0.58-3.92, P = 0.395). We provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS. Conclusion: Our findings provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS.

Angio-Long Noncoding RNA MALAT1 (rs3200401) and MIAT (rs1061540) Gene Variants in Ovarian Cancer.

The genotyping of long non-coding RNA (lncRNA)-related single-nucleotide polymorphisms (SNPs) could be associated with cancer risk and/or progression. This study aimed to analyze the angiogenesis-related lncRNAs MALAT1 (rs3200401) and MIAT (rs1061540) variants in patients with ovarian cancer (OC) using "Real-Time allelic discrimination polymerase chain reaction" in 182 formalin-fixed paraffin-embedded (FFPE) samples of benign, borderline, and primary malignant ovarian tissues. Differences in the genotype frequencies between low-grade ovarian epithelial tumors (benign/borderline) and malignant tumors and between high-grade malignant epithelial tumors and malignant epithelial tumors other than high-grade serous carcinomas were compared. Odds ratios (ORs)/95% confidence intervals were calculated as measures of the association strength. Additionally, associations of the genotypes with the available pathological data were analyzed. The heterozygosity of MALAT1 rs3200401 was the most common genotype (47.8%), followed by C/C (36.3%). Comparing the study groups, no significant differences were observed regarding this variant. In contrast, the malignant epithelial tumors had a higher frequency of the MIAT rs1061540 C/C genotype compared to the low-grade epithelial tumor cohorts (56.7% vs. 37.6, p = 0.031). The same genotype was significantly higher in high-grade serous carcinoma than its counterparts (69.4% vs. 43.8%, p = 0.038). Multivariate Cox regression analysis showed that the age at diagnosis was significantly associated with the risk of OC development. In contrast, the MIAT T/T genotype was associated with a low risk of malignant epithelial tumors under the homozygote comparison model (OR = 0.37 (0.16-0.83), p = 0.017). Also, MIAT T allele carriers were less likely to develop high-grade serous carcinoma under heterozygote (CT vs. CC; OR = 0.33 (0.12-0.88), p = 0.027) and homozygote (TT vs. CC; OR = 0.26 (0.07-0.90), p = 0.034) comparison models. In conclusion, our data provide novel evidence for a potential association between the lncRNA MIAT rs1061540 and the malignant condition of ovarian cancer, suggesting the involvement of such lncRNAs in OC development.

Association of Vitamin D Gene Receptor Polymorphism with Osteoporosis in Postmenopausal Women

Osteoporosis is a critical and complicated systemic musculoskeletal disorder that encompasses low bone density (LBD) and weakening of osseous tissue at a microarchitectural level. This predisposes to increased bone fragility and subsequent risk of fractures. It is frequently encountered in postmenopausal women and has also been seen in elderly men. Vitamin D synchronizes bone and calcium homeostasis in the body by modifying the transcription of target genes through the Vitamin D receptor (VDR) and thus aids calcium uptake and bone-forming proteins. The main objective of the present research was to study the relationship of single nucleotide polymorphisms (SNP) (rs1544410 G>A) of the VDR gene with postmenopausal women who have osteoporosis in a Pakistani cohort. A total of 100 postmenopausal women, 50 without osteoporosis to be in the control group, and 50 with osteoporosis as cases, were enrolled in this study. The patients had no immediate family connections with each other. All the patients underwent BMD measurements at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry scan for their diagnosis of osteoporosis based on World Health Organization (WHO) criteria (T score < -2.5 SD). A total of 25 participants had at least one allele of rs1544410, of which 14 were cases and 11 controls. The number of heterozygous and homozygous were present with similar ratios in both groups (p=0.973). Age was noted to be correlated with osteoporosis (OR: 1.06; 95%CI: 1.004-1.12), (P<0.031). It was also observed that cases had a notably lower weight than the control group (P<0.0001) and the overall body mass index of cases was significantly low in comparison to control (P<0.0001). Moreover, average BMD of femoral and BMD lumbar were notably greater among the control group (P<0.0001) as compared to cases. The SNP (rs1544410) is not significantly associated with BMD but significantly correlated with age which was identified as a risk factor while body mass index was found to be a protective factor for osteoporosis

Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease

ObjectivesThe prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association. MethodsThe study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death. ResultsDuring a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84–0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216). ConclusionsLower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.

Different sedentary behaviors, genetic susceptibility of hypertension, and new-onset hypertension: Mediating effects of body mass index and grip strength.

The association between different sedentary behaviors and hypertension risk remains unclear. We aimed to explore the relationship between different domains of sedentary behaviors and new-onset hypertension, investigate whether genetic susceptibility to hypertension modifies the relationship, and examine the extent to which the relationship is mediated by body mass index (BMI) and grip strength. 212 714 participants without baseline hypertension in the UK Biobank were enrolled. The three major sedentary behaviors (TV-watching, nonoccupational computer use, and driving) were measured using touch screen questionnaires. The primary outcome was new-onset hypertension. During a median follow-up of 11.9 years, 13 983 participants developed hypertension. There was a linear positive association between TV-watching time and new-onset hypertension (p for nonlinearity =0.868). A J-shaped association was found for nonoccupational computer use time and driving time with new-onset hypertension, with an inflection point of 0.5 h/day for both (both p for nonlinearity <0.001). Polygenetic risk scores for hypertension (based on 118 related single-nucleotide polymorphisms) did not significantly modify these associations (all p-interactions >0.05). Furthermore, the detrimental effects of long-term sedentary behaviors on hypertension were mediated by BMI by 21%-30%, and the beneficial effects of limited sitting time (within 0.5 h/day) for driving and nonoccupational computer use were mediated by grip strength by 6-25%. There was a positive association for hands-independence sedentary behavior (TV-watching), and a J-shaped association for hands-dependence sedentary behaviors (nonoccupational computer use and driving) with new-onset hypertension, regardless of genetic risks of hypertension. These relationships were partly mediated by BMI and grip strength.

Concomitant coronary artery disease development in identical twins: a case report and a systematic literature review

Abstract Case summary: Two 47-year-old monozygotic male twins presented to a tertiary hospital with chest pain (having a 3-month difference in their presentation). They were both smokers without any other standard modifiable risk factor or positive family history. Coronary angiograms of both twins demonstrated concordant coronary anatomy and obstructive CAD in two major epicardial coronary vessels with nearly identical lesions. Lipoprotein(a) [lp(a)] levels were substantially elevated in both twins (170 and 120 mg/dl respectively). Aiming to explain the almost identical CAD observed, next-generation whole-exome sequencing analyses were performed; however, no disease-causing CAD- or lp(a)-related mutation could be identified. Background The occurrence of CAD is strongly affected by genetic, epigenetic and environmental factors. Currently, a growing yet heterogeneous body of evidence reports the development of concomitant CAD in identical twins; however, no systematic approach has been attempted so far to gather and quantify the existing evidence. Methods A systematic literature review was conducted by searching for original studies in PubMed, WebOfScience and Scopus databases through February 28, 2023 to identify every study reporting the incidence of CAD in monozygotic twin pairs according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and predetermined eligibility criteria (https://doi.org/10.17605/OSF.IO/TWXKP). Results Our search yielded 28 eligible studies encompassing a total of 37 monozygotic twin pairs suffering from CAD and presenting (simultaneously most of them) with acute coronary syndrome (mean age of presentation: 46 years, male percentage: 78%). Coronary angiograms demonstrated lesion and anatomy concordance at a 86% and 79% of the twin pairs, respectively. Concordance of the standard modifiable (environmental) cardiovascular risk factors was identified in at least 75% of the twin pairs, whereas only 4 genetic polymorphisms were identified (i.e., erythrocyte/leucocyte, ACE, LDLR, APOB genes and HLA polymorphisms). Conclusion This is the first systematic literature review of studies reporting identical twin pairs who suffer concomitantly from CAD. Most pairs shared similar environmental risk factors; however, their premature CAD could not be sufficiently explained in most cases leading us to speculate underlying (non-recognized) epigenetic interplay. Monozygotic twin studies -unbiased by age effects- can provide insights into CAD heritability on the grounds of their ability to disentangle the traditional dyad of genetic and environmental factors. Given the limited evidence on disease-causing mutations in the eligible studies, future twin studies are warranted to shed light on non-investigated genetic polymorphisms [such as lp(a)-related single nucleotide polymorphisms] and investigate the within-pair epigenetic drift through novel biomarkers of epigenetic regulation.PRISMA flow diagram of the reviewConcordance of CAD-related risk factors

Advanced Skeletal Ossification Is Associated with Genetic Variants in Chronologically Young Beef Heifers.

Osteogenesis is a developmental process critical for structural support and the establishment of a dynamic reservoir for calcium and phosphorus. Changes in livestock breeding over the past 100 years have resulted in earlier bone development and increased physical size of cattle. Advanced skeletal maturity is now commonly observed at harvest, with heifers displaying more mature bone than is expected at 30 months of age (MOA). We surmise that selection for growth traits and earlier reproductive maturity resulted in co-selection for accelerated skeletal ossification. This study examines the relationship of single nucleotide polymorphisms (SNPs) in 793 beef heifers under 30 MOA with USDA-graded skeletal maturity phenotypes (A-, B-, C- skeletal maturity). Further, the estrogen content of FDA-approved hormonal implants provided to heifers prior to harvest was evaluated in association with the identified SNPs and maturities. Association tests were performed, and the impact of the implants were evaluated as covariates against genotypes using a logistic regression model. SNPs from the ESR1, ALPL, PPARGC1B, SORCS1 genes, and SNPs near KLF14, ANKRD61, USP42, H1C1, OVCA2, microRNA mir-29a were determined to be associated with the advanced skeletal ossification phenotype in heifers. Higher dosage estrogen implants increased skeletal maturity in heifers with certain SNP genotypes.

Vascular Endothelial Growth Factor Polymorphism rs699947 Is Associated with Neurostructural Phenotypes in Youth with Bipolar Disorder.

Background: Vascular endothelial growth factor (VEGF) may be relevant to bipolar disorder (BD) and brain structure. We evaluated VEGF rs699947 single-nucleotide polymorphism in relation to structural neuroimaging phenotypes in youth BD. Methods: We collected 3 T anatomical magnetic resonance images from 154 youth (79 BD and 75 healthy control [HC]) genotyped for VEGF rs699947. The participants were age (BD = 17.28 ± 1.40 and HC = 17.01 ± 1.83, t = -1.02, p = 0.31) and sex (BD = 63.3% females and HC = 52.0% females, χ2 = 2.01, p = 0.16) matched. Cortical thickness, surface area (SA), and volume were examined by region-of-interest (ROI) and vertex-wise analyses using general linear models (GLMs). ROI investigations selected for the prefrontal cortex (PFC), amygdala, and hippocampus. Vertex-wise analyses controlled for age, sex, and intracranial volume. Results: ROI results found lower PFC SA (p = 0.003, ηp2 = 0.06) and volume (p = 0.04, ηp2 = 0.03) in BD and a main effect of rs699947 on hippocampal volume (p = 0.03, ηp2 = 0.05). The latter two findings did not survive multiple comparisons. Vertex-wise analyses found rs699947 main effects on left postcentral gyrus volume (p < 0.001), right rostral anterior cingulate SA (p = 0.004), and right superior temporal gyrus thickness (p = 0.004). There were significant diagnosis-by-genotype interactions in the left superior temporal, left caudal middle frontal, left superior frontal, right fusiform, and right lingual gyri, and the left insular cortex. Posthoc analyses revealed the AA allele was associated with larger brain structures among HC, but smaller brain structures in BD for most clusters. Conclusions: Overall, we found preliminary evidence of divergent associations between BD and HC youth in terms of neurostructural correlates of VEGF rs699947 encompassing highly relevant frontotemporal regions.

LncRNA BCLET variant confers bladder cancer susceptibility through alternative splicing of MSANTD2 exon 1.

Alternative splicing (AS)-related single nucleotide polymorphisms (SNPs) are associated with risk of cancers, but the potential mechanism has not been fully elucidated. Two-stage case-control studies comprising 1630 cases and 2504 controls were conducted to investigate the association between the AS-SNPs and bladder cancer susceptibility. A series of assays were used to evaluate the functional effect of AS-SNPs on bladder cancer risk. We observed that SNP rs558814 A>G located in lncRNA BCLET (Bladder Cancer Low-Expressed Transcript, ENSG00000245498) can decrease the risk of bladder cancer (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.76-0.92, p = 3.26 × 10-4 ). Additionally, the G allele of rs558814 had transcriptional regulatory effects and facilitated the expression of BCLET transcripts, including BCLET-long and BCLET-short. We also found decreased BCLET expression in bladder cancer tissues and cells, and BCLET transcript upregulation substantially inhibited tumor growth of both bladder cancer cells and xenograft models. Mechanistically, BCLET recognized and regulated AS of MSANTD2 to participate in bladder carcinogenesis, preferentially promoting the production of MSANTD2-004. SNP rs558814 was associated with the expression of BCLET, which mainly increased the expression of MSANTD2-004 through AS of MSANTD2.

Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans.

Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study's objective is to evaluate SNP-SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP-SNP interactions were analyzed. None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP-SNP interaction pairs can predict PCa aggressiveness with a medium to large effect size. For the EA PCa patients, the interaction between rs1801133 (MTHFR) and rs2236225 (MTHFD1), and rs1801131 (MTHFR) and rs7587117 (SLC4A5) were significantly associated with aggressive PCa. For the AA PCa patients, the interaction of DHFR-19bp polymorphism and rs4652 (LGALS3) was significantly associated with aggressive PCa. These SNP-SNP interactions in the folate metabolism-related genes have a larger impact than SNP individual effects on tumor aggressiveness for EA and AA PCa patients. These findings can provide valuable information for potential biological mechanisms of PCa aggressiveness.

A study of genetic variants in patients with ischemic stroke in human rat gene orthologues

To study the associations of nine genetic variants with the risk and dynamics of recovery (outcome) of ischemic stroke (IS) using the developed protocol for the search for genomic markers based on a bioinformatic approach to the study of single nucleotide polymorphisms (SNPs) in human orthologues of rat genes differentially expressed under conditions of induced cerebral ischemia. We identified and analyzed nine SNPs in 553 Russians (331 IS patients and 222 controls). The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity. Functional recovery after stroke was assessed using the modified Rankin scale (mRS). The principles of selection of polymorphic markers analyzed in the study were determined according to the protocol developed by us earlier. Selected SNP tags were genotyped using real-time polymerase chain reaction (PCR) TaqMan. The relationship of SNP with both the risk of IS and the dynamics of its recovery was investigated. SNP rs66782529 (LGALS3) was associated with negative IS outcomes (p=0.048). SNPs rs62278647 and rs2316710 (PTX3) were significantly associated with IS risk (p=0.000029 and p=0.0025, respectively). The associations for rs62278647 and rs2316710 were found only in females, suggesting a gender-related PTX3 polymorphism. This study not only reveals some new genetic links to IS and its consequences, but also shows how the study of gene variations in a rat model of cerebral ischemia can be useful in the search for genetic markers of this disease in humans.

Effect of breastfeeding on the HMGA2 single nucleotide polymorphisms in relation to first primary tooth emergence among Iraqi infants

Abstract Backgrounds: Breastfeeding provides a large group of functional components that improve the infant’s health and development. additionally, the impact of human milk and genetic variants on complicated outcomes has also been the subject of several gene–nutrition interaction studies. This could also play a key part in the kinship that exists between offspring and their parents. Objectives: The purpose of this study was to compare breastfeeding to infants who were fed formula in order to determine if human milk affected the timing of teething in relation to genetic polymorphisms. Materials and Methods: This study is a cross-sectional comparative study concerning genetic analysis with a prospective view concerning the timing of eruption. The chosen sample included 40 breastfed infants and 40 infants who consumed formula milk. It was compiled from Baghdad’s health centers. For the genetic analysis, DNA samples were obtained from saliva throughout the buccal swab. Standard DNA extraction and real-time PCR techniques have been used according to the manufacturer’s instructions for the Quick-DNA™ MiniPrep kit (catalog nos. D3024 and D3025). For the whole sample, clinical examination and monitoring for emerging teeth were performed using a particular criterion. Results: findings showed that there were highly significant differences between breastfeeding and early eruption time for the first primary tooth. Also, there was a significant association between single nucleotide polymorphisms in the heterozygous AG genotype and eruption time. Conclusion: The results of the current study may support the genetic influence of breast milk on early primary teeth eruption when juxtaposed with infants fed formula.

Genetic insights into the risk of snoring on stroke and ischemic stroke: A single-variable and multivariable Mendelian randomization.

Multiple risk factors of stroke have been identified in previous studies; however, the causal role of snoring in the onset of stroke is less investigated. To clarify the causal association of snoring on stroke and its subtypes, this study is performed. The single nucleotide polymorphisms in relation to snoring were retrieved from the UK biobank cohort with 408,317 participants. The data for stroke and its subtypes of European ancestry (67,162 cases and 453,702 controls) were obtained from the MEGASTROKE consortium. In single-variable Mendelian randomization (SVMR) and multivariable MR (MVMR) analyses, inverse variance weighting was used as the primary estimate, complemented with sensitivity analyses more robust to pleiotropy. Genetically predicted snoring increased the risk of stroke (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.19-6.08, P = 0.016) and ischemic stroke (IS) (OR = 2.82, 95% CI = 1.23-6.44, P = 0.013), but not large artery stroke (LAS) (OR = 3.02, 95% CI = 0.31-29.44, P = 0.339), cardioembolic stroke (CES) (OR = 1.51, 95% CI = 0.58-3.92, P = 0.395). We provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS. Our findings provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS.

Association of vitamin D gene polymorphisms and serum 25-hydroxyvitamin D in Chinese women of childbearing age

To analyze the relationship between vitamin D(VitD)-related single nucleotide polymorphism(SNP) and 25-hydroxyvitamin D(25(OH) D) levels and VitD nutritional status. A total of 1507 women of childbearing age aged 18-45 were selected from the sample bank of "2015 Chinese adult chronic disease and nutrition monitoring". Basic information(including region, season, age, height, weight, etc. ) of the subjects was collected. The SNPs related to VitD metabolism were screened, and the improved multiple ligase detection reaction was used for SNP testing. Liquid chromatography tandem mass spectrometry was used to determine the serum 25(OH)D concentration. The effects of genotypes on 25(OH)D level and VitD deficiency were analyzed by generalized linear model and binary logistic regression model, respectively. After adjusting for latitude, region, region type, season and age, CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 were associated with serum 25(OH)D levels in women of childbearing age. The risk of VitD deficiency in individuals carrying GG genotype at rs2282679 was significantly higher than that in individuals carrying TT genotype(OR=2.466, 95%CI 1.690-3.598, P&lt;0.001), and the risk of VitD deficiency in individuals carrying A allele at rs2228570 was lower than that in individuals carrying G allele(OR_(AA)=0.625, 95%CI 0.446-0.876, P_(AA)=0.006;OR_(GA)=0.661, 95%CI 0.502-0.869, P_(GA)=0.003). The genotype distribution of CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 may be related to serum 25(OH)D level or VitD nutritional status of Chinese women of childbearing age.

Structure-Switchable Hairpin-Powered Exponential Replications for Sensing Attomolar microRNA-Related Single Nucleotide Polymorphisms in Human Cancer Tissues with Zero Background.

MicroRNA (miRNA)-related single-nucleotide polymorphisms (miR-SNPs) are a novel class of genetic variations involved in multiple cellular functions, and they have emerged as promising biomarkers for cancer diagnostics and prognostics. Herein, we demonstrate for the first time the structure-switchable hairpin-powered exponential replications for sensing attomolar miR-SNPs in human cancer tissues with zero background. In the presence of target miR-196a2T, hairpin probes (i.e., HP1 and HP2) are splinted together to construct the dumbbell-shaped probe (DSP) with SplintR ligase catalysis. Once the DSP is formed, the self-primed polymerization extension and linear FIP/BIP-primed strand displacement DNA synthesis (SDS) are automatically repeated to activate self-circulated exponential amplification, producing large amounts of double-stranded DNAs (dsDNAs) which can be real-time monitored using SYBR Green I. This nanodevice can detect miR-196a2T with an ultralow detection limit of 2.46 aM; distinguish rare miR-196a2 SNP with a selectivity factor of 0.001%; and even profile miR-196a2T in human tissues for nonsmall cell lung cancer (NSCLC) diagnosis, risk assessment, and cancer type prediction. Notably, this nanodevice can be rapidly and homogeneously used in one tube in a real-time and label-free manner, providing a powerful point-of-care platform for noninvasive diagnostics and prognostics of miR-SNPs-related human cancers.

A functional microRNA binding site variant in IL-23R gene in systemic lupus erythematosus and rheumatoid arthritis: is there any correlation?

IL-23 receptor (IL-23R) dysregulation has been shown to have critical roles in pathogenesis of different autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) via suppression of regulatory T cells (Tregs) as well as differentiation, expansion, and survival of T helper 17 (Th17) cells, followed by upregulation of interleukin 17 (IL-17). Here, we assessed the association of a functional microRNAs (miRNAs)-related single nucleotide polymorphism (miR-SNPs: rs10889677) in IL-23R, which was correlated with its overexpression and increased risk for SLE and RA in the Iranian population. Genotype and allele distribution of rs10889677 variant were investigated in 105 RA patients, 100 SLE cases and 105 healthy controls via polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Our findings suggested that AA genotype, but not AC genotype, was associated with increased risk of RA (AA vs. CC; OR: 3.27; 95%CI [1.467-7.551]). The allele A was more frequent in RA group compared to controls (A allele vs. C allele; OR: 1.92; 95%CI [1.282-2.894]). This common variant was not significantly correlated with SLE risk in our population (P > 0.05). However, stratification analysis indicated that RA patients with AA genotype show higher serum concentration levels of C-reactive protein (CRP) (P: 0.008). No obvious correlation was noticed between different genotypes in SLE cases, except for a slight difference in terms of oral ulcer manifestation incidence (P: 0.038). This study suggests a significant relationship between rs10889677 variant in IL-23R with increased risk of RA and some clinical features in RA and SLE patients.

Alzheimer's disease related single nucleotide polymorphisms and correlation with intracerebral hemorrhage incidence.

Apolipoprotein E alleles have been associated with both Alzheimer’s disease (AD) and intracerebral hemorrhage (ICH). In addition, ICH is associated with a markedly high risk of subsequent dementia compared to other subtypes of stroke. We sought to evaluate if other genetic markers for AD were also associated with ICH. We examined whether published AD risk single nucleotide polymorphisms (SNPs) and haplotypes were associated with ICH utilizing genome-wide association study data from 2 independent studies (genetic and environmental risk factors for hemorrhagic stroke [GERFHS] study and genetics of cerebral hemorrhage with anticoagulation [GOCHA]). Analyses included evaluation by location of ICH. GERFHS and GOCHA cohorts contained 745 ICH cases and 536 controls for analysis. The strongest association was on 1q32 near Complement receptor type 1 (CR1), where rs6701713 was associated with all ICH (P = .0074, odds ratio [OR] = 2.07) and lobar ICH (P = .0073, OR = 2.80). The 51 most significant 2-SNP haplotypes associated with lobar ICH were identified within the Clusterin (CLU) gene. We identified that variation within CR1 and CLU, previously identified risk factors for AD, and are associated with an increased risk for ICH driven primarily by lobar ICH. Previous work implicated CR1 and CLU in cerebral amyloid clearance, the innate immune system, and cellular stress response.

Genome-wide association study reveals that GhTRL1 and GhPIN8 affect cotton root development.

Two regions located at chromosome A05 and D04 were found to be significantly associated with 0-0.5mm and 0.5-2mm diameter roots, respectively, and two candidate genes related to root development were identified. Roots absorb water and nutrients, and play an important role in plant growth. However, there are few genetic developmental studies on cotton root structural traits. In this study, we used 200 upland cotton (Gossypium hirsutum L.) varieties to analyze the phenotypic variation of 43 traits. A total of 2001 related single-nucleotide polymorphism (SNP) sites located within or near 1046 genes were detected through a genome-wide association study (GWAS). The 32 root traits were linked to SNPs that corresponded to 317 nonrepetitive genes. For SNPs associated with root length and 0-0.5mm diameter root traits, a significant peak appeared on chromosome A05 (between 21.91 and 22.24Mb). For SNPs associated with root surface area, root volume and 0.5-2mm diameter root traits, a significant peak appeared on chromosome D04 (between 7.35 and 7.70Mb). Within these two key regions, SNPs were detected in the promoter and coding regions of two candidate genes, GhTRL1-A05 and GhPIN8-D04. The expression levels of these two genes also changed significantly according to transcriptome sequencing and quantitative real-time PCR (qRT-PCR). After silencing the GhTRL1 and GhPIN8 genes via virus-induced gene silencing (VIGS), we found that the plants expressing TRV2::GhTRL1 and TRV2::GhPIN8 had a reduced root length, surface area. Moreover, the contents of cis-12-oxo-phytodienoic acid (cis-OPDA), isopentenyl adenosine (iPR) and cis-zeatin (cZ) in the roots of the plants expressing TRV2::GhTRL1 decreased. This study contributes to the cultivation and improvement of cotton varieties.