Single Nucleotide Polymorphisms Polymorphisms Research Articles

The potential up-regulation risk of 3′ UTR SNP (rs10787760 G > A) for the VAX1 gene is associated with NSCLP in the northwest Chinese population

AimsTo investigate the association between single nucleotide polymorphisms (SNPs) in 3′UTR region of VAX1, SYT14 and PAX7 genes and the risk of non-syndromic cleft palate (NSCLP) in a northwest Chinese population. Main methodsA case-control study was conducted in 406 normal controls and 399 NSCLP patients. Using iMLDRTM genotyping technology, eight SNPs of three genes ((rs10787760, rs7086344 at VAX1), (rs1010113, rs851114, and rs485874 at PAX7), and (rs61820397, rs4609425, rs12133399 at SYT14)) were genotyped to investigate the differences in alleles and genotype distribution frequencies between NSCLP patients and healthy controls. RNA Folding Form software was used to predict RNA secondary structure and expression vectors were constructed to explore the function of the relevant SNP. The effect of SNP polymorphism of gene transcription and translation was assessed using qPCR and Western blot analysis.Key findings.Among the eight SNPs of three genes, rs10787760 of VAX1 gene was found to be associated with an increased risk of NSCLP (OR = 1.341, CI = 1.004–1.790) and the GA genotype of rs10787760 increased the risk of cleft lip and/or palate (CL/P) about 1.42 times (p < 0.05), and carrying the A allele might increase the risk of NSCL/P in male (OR = 1.356, 95 % CI = 1.010–1.823). But there was no association observed with cleft palate only (CPO). Cell function experiments revealed that the G to A mutation in rs10787760 up-regulated GFP-VAX1 transcriptional level by 2.39 and 3.13 times in two cell lines respectively, and enhance the protein expression of the VAX1 gene further. RNA secondary structure study showed that the rs10787760 (G > A) had two different secondary structures in 3′UTR region. SignificanceThe rs10787760 variant in the 3′UTR region of VAX1 gene is associated with CL/P in northwest Chinese population. We hypothesize that the machanism of it might be caused by the RNA differenct fold in the 3′UTR region caused by the polymorphism of the gene. Level of evidenceOriginal Reports.

Interferon Regulatory Factor 5 Gene Polymorphisms and mRNA Expression Levels Are Associated with Neuromyelitis Optica Spectrum Disorder.

Interferon regulatory factor 5 (IRF5) is a critical transcription factor in the toll-like receptor signaling pathway. It is associated with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. However, the relationship between the functional single nucleotide polymorphisms (SNPs) of IRF5 and its mRNA expression level in patients with neuromyelitis optica spectrum disorder remains unclear. The present study aimed to investigate the relationship between polymorphisms and mRNA expression levels of the IRF5 gene with the incidence of neuromyelitis optica spectrum disorder (NMOSD) in northern Chinese Han people. Two loci of the IRF5 gene (rs2004640 and rs2280714) of 164 patients with NMOSD and 269 healthy subjects were genotyped using the multiple SNaPshot technique. The frequencies of alleles, genotypes, and haplotypes were compared. Stratified analysis was performed according to age, sex, AQP4 status, onset age, and Expanded Disability Status Scale (EDSS) score. The IRF5 mRNA levels in peripheral blood mononuclear cells (PBMCs) of 64 NMOSD patients (32 patients in the acute stage and 32 patients in the remission stage) and 35 healthy subjects were detected by real-time PCR. The association of SNP polymorphisms with the mRNA expression level was determined by nonparametric tests. Allele and genotype frequency distributions of rs2004640 showed significant differences between both groups. Compared to healthy controls, the frequency of rs2004640 T allele markedly increased in patients (OR = 1.51, 95% CI = 1.09-2.08, P = 0.005). Minor allele T and GT genotype of rs2004640 that significantly increases the risk of NMOSD were discovered using genetic inheritance models (codominant, dominant, and overdominant) and haplotype analyses. Subsequent haplotype analyses revealed that the major haplotype "T-A" containing the risk alleles (the SNP sequence of the alleles was rs2004640 and rs2280714) had adverse effects on NMOSD. Based on the stratification analysis according to the EDSS score, the GT genotype frequency in the EDSS ≥ 4 group (38.2%) was markedly lower than that in the EDSS < 4 group (61.8%) (OR = 0.32, 95% CI = 0.15-0.68, P = 0.0054), with a significant difference. The IRF5 mRNA expression level was increased in NMOSD patients compared to that in normal subjects. IRF5 gene polymorphisms may be tightly associated with the genesis and progression of NMOSD in northern Chinese Han people. IRF5 mRNA expression was increased in patients with NMOSD and significantly increased in patients with acute phase. Perhaps IRF5 expression levels can be used as a predictor of disease activity in the future.

Investigation of lncRNA PART1 SNP (rs8176070) polymorphism in Turkey knee osteoarthritis patient population by DNA sequence analysis

Osteoarthritis (OA) is a chronic disease characterised by cartilage degradation, synovial inflammation, subchondral bone remodelling, and osteophyte formation. The aim of this knee OA-control study was to investigate the association between a single nucleotide polymorphism (SNP) (rs8176070) of the long non-coding RNA gene (lncRNA) PART1 and knee OA in the Turkish population. The study population consisted of 102 knee OA and 81 controls. We isolated genomic DNA from peripheral blood and performed PCR-RFLP reactions for genotyping of lncRNA PART1. Sanger DNA sequencing was used to genotype the groups. The results showed that the mean age and gender of the knee OA group were significantly higher than those of the control group (p < 0.05). Body mass index (BMI) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were also higher in the case group than in the control group (p ≤ 0.001). However, no significant association was found between the lncRNA SNP PART1 (rs8176070) and knee OA for genotypes BB, Bb, and bb (p > 0.05). Further studies with larger populations and more SNPs associated with OA may be needed to demonstrate a positive association.

Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer

BackgroundCancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients.MethodsThe SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF–MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0).ResultsStratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death.ConclusionRs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.

Association of the rs17782313, rs17773430 and rs34114122 Polymorphisms of/near MC4R Gene with Obesity-Related Biomarkers in a Spanish Pediatric Cohort.

Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.

A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms.

Cigarette smoking (CS) is a major cause of various serious diseases due to tobacco chemicals. There is evidence suggesting that CS has been linked with the DNA damage repair system, as it can affect genomic stability, inducing genetic changes in the genes involved in the repair system, specifically the nucleotide excision repair (NER) pathway, affecting the function and/or regulation of these genes. Single nucleotide polymorphism (SNP), along with CS, can affect the work of the NER pathway and, therefore, could lead to different diseases. This study explored the association of four SNPs in both XPA and XPC genes with CS in the Saudi population. The Taq Man genotyping assay was used for 220 healthy non-smokers (control) and 201 healthy smokers to evaluate four SNPs in the XPA gene named rs10817938, rs1800975, rs3176751, and rs3176752 and four SNPs in the XPC gene called rs1870134, rs2228000, rs2228001, and rs2607775. In the XPA gene, SNP rs3176751 showed a high-risk association with CS-induced diseases with all clinical parameters, including CS duration, CS intensity, gender, and age of smokers. On the other hand, SNP rs1800975 showed a statistically significant low-risk association with all clinical parameters. In addition, rs10817938 showed a high-risk association only with long-term smokers and a low-risk association only with younger smokers. A low-risk association was found in SNP rs3176752 with older smokers. In the XPC gene, SNP rs2228001 showed a low-risk association only with female smokers. SNP rs2607775 revealed a statistically significant low-risk association with CS-induced diseases, concerning all parameters, except for male smokers. However, SNP rs2228000 and rs1870134 showed no association with CS. Overall, the study results demonstrated possible significant associations (effector/and protector) between CS and SNPs polymorphisms in DNA repair genes, such as XPA and XPC, except for rs2228000 and rs1870134 polymorphisms.

Genetic variation and population structure of Oryza sativa accessions in the AfricaRice collection and development of the AfricaRice O. sativa Core Collection

AbstractGenetic diversity studies provide an increased understanding of genebank collections and enhance their use for improving global food security. This study explores the genetic variation and population structure of 5738 rice (Oryza sativa L.) accessions representing 39.6% of the O. sativa collection conserved in the AfricaRice genebank of which 74.0% originated from African countries. These accessions were genotyped with 25,904 polymorphic DArTseq‐based single nucleotide polymorphisms (SNPs). Genetic distances between pairs of accessions indicate high variability, with 21.0% of pairs being moderately distant and 78.2% highly distant from each other. The genotyped accessions are traditionally grown in six different agro‐ecologies from 73 countries. Using neighbor‐joining tree, principal component, and model‐based population structure analyses, the accessions were divided into four genotypic groups representing the two O. sativa subspecies, Japonica (787 accessions) and Indica, which were further divided into landraces (1879 accessions), and improved cultivars (3027 accessions), and a fourth small group of admixed accessions. Subclusters identifying a specific agro‐ecology (upland, lowland, and mangrove swamp) or originating country were noted. Using the maximum length sub‐tree method, we selected 10% of the total accessions to form the “AfricaRice O. sativa Core Collection” (AROSCC). The subset of 600 O. sativa accessions captures more than 95% of the SNP polymorphisms in the entire collection. The AROSCC is an important resource to support pre‐breeding and rice improvement programs around the world.

Estrogen receptor alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in pashtun population of Khyber Pakhtunkhwa.

Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in patients of Khyber Pakhtunkhwa. A total of 312 females including 162 breast cancer patients and 150 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR. Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.21, OR = 1.27, CI = 0.87 to 1.87) and containing genotypes CC (P = 0.68, OR = 1.24, CI = 0.42 to 3.68) and TC (P = 0.23, OR = 1.32, CI = 0.83 to 2.13) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P < 0.0001, OR = 2.42, CI = 1.74 to 3.38) and corresponding genotypes GA (P = 0.0001, OR = 2.55, CI = 1.62 to 4.03) and AA (P = 0.02, OR = 2.20, CI = 1.12 to 4.34) were significantly associated with higher risk of breast cancer. Moreover, ESR1-rs2234693 was significantly (P < 0.05) associated with family history, stages, PR status, ER status and luminal B. The ESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P > 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A. It is concluded that ESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation of ESR1 polymorphism, ESR1 existing and other SNPs need to be investigated in diverse data sets.

Long-Amplicon Single-Molecule Sequencing Reveals Novel, Trait-Associated Variants of VERNALIZATION1 Homoeologs in Hexaploid Wheat.

The gene VERNALIZATION1 (VRN1) is a key controller of vernalization requirement in wheat. The genome of hexaploid wheat (Triticum aestivum) harbors three homoeologous VRN1 loci on chromosomes 5A, 5B, and 5D. Structural sequence variants including small and large deletions and insertions and single nucleotide polymorphisms (SNPs) in the three homoeologous VRN1 genes not only play an important role in the control of vernalization requirement, but also have been reported to be associated with other yield related traits of wheat. Here we used single-molecule sequencing of barcoded long-amplicons to assay the full-length sequences (∼13 kbp plus 700 bp from the promoter sequence) of the three homoeologous VRN1 genes in a panel of 192 predominantly European winter wheat cultivars. Long read sequences revealed previously undetected duplications, insertions and single-nucleotide polymorphisms in the three homoeologous VRN1 genes. All the polymorphisms were confirmed by Sanger sequencing. Sequence analysis showed the predominance of the winter alleles vrn-A1, vrn-B1, and vrn-D1 across the investigated cultivars. Associations of SNPs and structural variations within the three VRN1 genes with 20 economically relevant traits including yield, nodal root-angle index and quality related traits were evaluated at the levels of alleles, haplotypes, and copy number variants. Cultivars carrying structural variants within VRN1 genes showed lower grain yield, protein yield and biomass compared to those with intact genes. Cultivars carrying a single vrn-A1 copy and a unique haplotype with a high number of SNPs were found to have elevated grain yield, kernels per spike and kernels per m2 along with lower grain sedimentation values. In addition, we detected a novel SNP polymorphism within the G-quadruplex region of the promoter of vrn-A1 that was associated with deeper roots in winter wheat. Our findings show that multiplex, single-molecule long-amplicon sequencing is a useful tool for detecting variants in target genes within large plant populations, and can be used to simultaneously assay sequence variants among target multiple gene homoeologs in polyploid crops. Numerous novel VRN1 haplotypes and alleles were identified that showed significantly associations to economically important traits. These polymorphisms were converted into PCR or KASP assays for use in marker-assisted breeding.

P-523 rs2277698 Single nucleotides polymorphisms in tissue inhibitors of metalloproteinases 2 (TIMP2) affected clinical outcomes of women undergoing in vitro fertilization

Abstract Study question Is there any association between clinical outcomes of women undergoing in vitro fertilization (IVF) and the polymorphic variants of matrix metalloproteinases (MMPs) or tissue inhibitors of metalloproteinases (TIMPs)? Summary answer Our findings suggested that clinical outcomes of women undergoing IVF were associated with rs2277698 SNPs in TIMP2. What is known already The extracellular matrix proteolytic machinery is one of the most important mechanisms for regulating trophoblast invasion. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which are involved in the extracellular matrix proteolysis process, have the ability to regulate the degradation of the extracellular matrix and play a critical role in trophoblast invasion. Study design, size, duration A prospective study was composed of 1014 women undergoing their first fresh IVF cycle with non-donor from January 2014 to December 2015. Participants/materials, setting, methods The present study was carried out in Lee Women’s Hospital, Taiwan. DNA was extracted from the peripheral blood of all participants, and the SNPs were genotyped by real-time polymerase chain reaction. The effects of the following three single nucleotide polymorphisms (SNPs) on IVF outcomes were explored: TIMP1 (rs4898 C/T), TIMP2 (rs2277698 C/T) and MMP2 (rs243865 C/T). The SNP genotype, correlation with clinical pregnancy, embryo implantation, abortion and live birth rates of IVF were analyzed. Main results and the role of chance In the analysis of 1014 patients attempting their first cycle of IVF, the genotypes frequencies of the study population showed a statistically significant association between TIMP2 (rs2277698 C/T) and clinical outcome. For TIMP2 polymorphisms, women with wild genotype (CC) hadhigher clinical pregnancy rate (34.8% v.s 28.0%; p = 0.032), embryo implantation rate (19.4% v.s 15.4%; p = 0.009), live birth rate (29.8% v.s 22.1%; p = 0.006), and lower abortion rate (7.0% v.s 17.1%; p = 0.005) compared women with CT/TT genotype. On the other hand, the clinical outcomes in different TIMP1 or MMP2 gene polymorphisms groups were no statistically significant difference. Limitations, reasons for caution The size number of the study samples. Wider implications of the findings This study showed that the TIMP2 SNP polymorphisms CT/TT was associated with low trend of clinical outcomes. The mechanism of TIMP2 gene T allele affected the outcomes of IVF remains to be determined. Further studies should focus on the mechanism of these associations in a larger, more heterogeneous cohort. Trial registration number CS13194

AN UPDATED REVIEW IN CORRELATING FAT MASS OBESITY ASSOCIATED GENETIC POLYMORPHISM IN WOMEN WITH POLYCYSTIC OVARIAN CONDITIONS

Women with Polycystic ovarian condition (PCOS) are reported to have obesity, which essentially influences the disorder's associated with insulin resistance, type 2 diabetes and cardiovascular disorders. PCOS is a problem of endocrine abnormality in women between the ages of 14-44. In this paper we review on recent methods in genotyping of fat mass obesity (FTO) associated gene single nucleotide polymorphism and its relationship with PCOS. Literature survey indicated that in diagnosis of PCOS, blood tests were normally used in gene polymorphism investigations and DNA tests were used for genotyping examination. The quick detection by polymerase chain reaction (PCR) amplification is one of the commonest tests for identifying single nucleotide polymorphism (SNP) for FTO traits which is being routinely used to understand the frequency of SNP polymorphism in a given set of population in various countries and in ethnic groups. Worldwide, extensive investigations were carried out to analyze the genotypes of FTO traits and its association in understanding the etiology of PCOS. Such literature surveys are beneficial in developing simple PCOS diagnostic methods and finding new approaches in therapeutic interventions. In this review paper, we highlight the genetic basis and importance of testing the FTO parameter in understanding the pathogenesis and the management of PCOS.

High soluble HLA-DQB2 levels in posttransplant serum are associated with kidney graft dysfunction.

HLA-DQB2 is a gene of limited polymorphism, with unknown function that presents at least two transcript variants: v1, which encodes the full-length beta-chain, and v2, which lacks exon 4 and could give rise to a soluble protein. We previously showed a strong correlation between high v2 expression in preimplantation biopsies (PIB) of kidneys from young (18- to 49-year olds) but not from old, deceased donors and 1-year posttransplant low (estimated glomerular filtration rate<45ml/min/1.73 m2 ) graft function (GF). In this study, we aimed to investigate the impact of posttransplant soluble HLA-DQB2 (sDQB2) serum levels, v1 expression in PIB, and recipient HLA-DQB2 rs7453920 A/G polymorphism on GF. sDQB2 was evaluated by enzyme-linked immunosorbent assay in sera from 114 recipients, collected at least 1 year (median 2.1 years) after transplantation. Higher sDQB2 levels were observed in recipients of kidneys from young, but not from old, donors that had a ≥30% decline in GF within 1 year after blood collection for sDQB2 determination. Among the 15 recipients of kidneys from young donors with sDQB2 ≥ 1.52ng/ml, 40% presented a ≥30% decline in GF, whereas this occurred in none of the 43 recipients with lower sDQB2 levels (p=0.007; OR: 36.5). Expression of HLA-DQB2 variant 1, measured by reverse transcription-polymerase chain reaction (RT-PCR) in 92 PIB from young or old donors, did not significantly differ between transplants with high or low 4-year GF. HLA-DQB2 rs7453920 single nucleotide polymorphism (SNP) frequencies did not significantly differ between recipients with low or high 4-year GF. We conclude that HLA-DQB2 variant 1 expression in PIB and recipient rs7453920 SNP polymorphism are not associated with graft outcome. On the other hand, the association, in transplants of kidneys from young donors, between high posttransplant serum sDQB2 levels and decline in GF is a very interesting finding that deserves a validation study in a larger cohort.

Association of SNP polymorphisms with productivity in cattle of Auliekol breed

The relevance of the research of the possibilities of using complete-genome analysis of associations in breeding programs with cattle of Auliekol breed, which bred in the Republic of Kazakhstan is dictated by the increasing needs of breeding in fast methods of selecting highly productive animals, from the one hand, and the expediency of working with breeding material adapted to local climatic feed conditions, from the other. Auliekol breed being the result of crossbreeding three breeds of beef productivity such as Aberdeen Angus, Charollais and Kazakh White-headed is of considerable interest from the point of view of breeding possibilities. The purpose of the research was to study the association of SNP polymorphisms with beef productivity in cattle of Auliekol breed. The results of the search and selection of breed-specifi c single nucleotide polymorphism (SNP) marking increased beef productivity based on DNA typing data of animals using the GGP Gene Search biochip of cattle 150K (Illumina Inc., USA) on the example of Auliekol breed have been presented in the article. As a result of the carried out research using the GeneSeek biochip beef 150K, unique SNP haplotypes corresponding to potential QTL in cattle of Auliekol breed on chromosomes: 1, 5 and 14 have been determined. Twelve breed–specific candidate genes have been identified, which belong to gene networks regulating cellular processes, biological regulation, metabolic processes, and growth and development processes. Five SNP markers of increased beef productivity in cattle of Auliekol breed have been identified such as allele C (rs108957811), allele T (rs134860368), allele C (rs135948785), allele T (rs435135552), allele A (rs720275361) in the myostatin gene (myostatin (MSTN).

Haplotypes of single cancer driver genes and their local ancestry in a highly admixed long-lived population of Northeast Brazil.

Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan.

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.

Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population

BackgroundRheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.ResultsOur results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age > 54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.ConclusionsOur study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.

NAT2 Gene rs1041983 is Associated with Anti-Tuberculosis Drug Induced Hepatotoxicity Among Pediatric Tuberculosis in Bandung, Indonesia.

BackgroundAs pediatric tuberculosis (TB) globally is still reported challenging in diagnosis, to date, a lot of efforts have been established to eliminate the disease including proper treatment regimen using anti-TB drugs. However, antituberculosis drug-induced hepatotoxicity (ADIH) is known to interfere the success of the prescribed therapy. ADIH was found to be correlated with polymorphisms of NAT2 gene, that is responsible to transcript the NAT2 enzyme, a metabolizer of isoniazid (INH). The most common NAT2 gene polymorphisms in Asian population associated with ADIH are rs1041983, rs1799929, rs1799930 and rs1799931. The study aimed to investigate the 4 single nucleotide polymorphisms (SNPs) in pediatric TB that experienced ADIH.MethodsWe conducted a case–control study comparing 31 each of pediatric TB experience with and without ADIH. All pediatric TB was selected from 451 pediatric TB Registry of Respirology Division, Department of Child Health Faculty of Medicine Universitas Padjadjaran/Dr Hasan Sadikin Hospital during January 2016 to July 2018. Genomic DNA PCR and sequencing to identify polymorphisms of rs1041983, rs1799929, rs1799930 and rs1799931 were performed in both groups. Data analysis was performed using the Epi info Ver. 7 software.ResultsThirty-one pediatric TB experiences with and without ADIH were enrolled in this study. SNP rs1041983 significantly affected the occurrence of ADIH (OR 2.39, CI 95% (1.15–4.96), p=0.019). The rs1799929, rs1799930 and rs1799931 did not significantly affect the occurrence of ADIH (p=0.133, p=0.150 and p=0.659, respectively).ConclusionPolymorphism SNP rs1041983 had association with the occurrence of ADIH.

Association Between TPM1 Gene Polymorphisms and Idiopathic Congenital Talipes Equinovarus Risk in a Chinese Population.

Background: Idiopathic congenital talipes equinovarus (ICTEV) is one of the most common congenital deformities of children, and dysplasia of the striated muscle may be one of the causes of ICTEV. Previous studies have shown that polymorphisms of the rs4075583 SNP in the tropomyosin gene 1 (TPM1) were associated with ICTEV in Caucasian children. However, there are no studies investigating the correlations of TPM gene polymorphisms with the risk of ICTEV in Chinese children. Methods: We conducted a case-control study, including 430 children with ICTEV and 891 ICTEV-free children. We explored the potential correlations of three TPM gene polymorphisms (TPM1/rs4075583 G>A, tropomyosin gene 2 (TPM2)/rs2145925 C>T, and TPM2/rs2025126 G>A) with ICTEV risk. The three single nucleotide polymorphisms (SNPs) were genotyped using a TaqMan method. We calculated the odds ratios (ORs) and adjusted ORs and their 95% confidence intervals (CIs) to explore the associations between these selected SNP polymorphisms and ICTEV. Results: TPM1 rs4075583 A was found to be associated with an increased ICTEV risk (AA vs. GG: adjusted OR = 1.70, 95% CI = 1.15-2.49, p = 0.007; and GG/GA vs. AA: adjusted OR = 1.62, 95% CI = 1.14-2.31, p = 0.0071) after adjusting for age and sex. In addition, a risk effect of rs4075583 GA/AA with ICETV was observed for patients with affected right feet (adjusted OR = 1.62, 95% CI = 1.10-2.39, p = 0.014) in the stratified analysis. However, there were no significant differences in the risk for ICTEV associated with the rs2145925 and rs2025126 polymorphisms. Conclusion: These results indicate that the TPM1 rs4075583 G > A polymorphism is associated with ICTEV risk in a southern Chinese population; however, this finding needs to be confirmed in larger studies and through mechanistic studies.

Association of dipeptidyl peptidase IV polymorphism, serum lipid profile, and coronary artery stenosis in patients with coronary artery disease and type 2 diabetes.

Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.

Identification of CXCL8c.105A>G and CXCL8c.210C>T polymorphism in Polish HF cattle

Background: Bovine chemokine C-X-C motif legend 8 (CXCL8) also known as interleukin 8 (IL8) is a chemotactic factor that attracts neutrophils, basophils, and T-cells, in response to an inflammatory stimulus. The aim of this study was to investigate the novel single nucleotide polymorphisms (SNPs) located at the promoter region of CXCL8 gene in Polish Holstein Friesian (HF) bulls.Methods: Genotypic profiling of CXCL8c.105A&gt;G and CXCL8c.210C&gt;T SNP polymorphism were carried out by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) methods using HpyCH4VI and RsaI restriction enzymes. Polymorphism study was conducted on 151 randomly selected Polish HF bulls.Results: The genotype frequencies of CXCL8c.105A&gt;G SNPs polymorphism in the investigated Polish HF bulls were observed as 0.24%, 0.5% and 0.26% respectively, whereas, the genotype frequencies of CXCL8c.210C&gt;T SNPs polymorphism were observed as 0.27%, 0.5% and 0.23% respectively. Overall, the allele frequencies were recorded higher for “G’ allele for CXCL8c.105A&gt;G and “C” allele and CXCL8c.210C&gt;T SNP polymorphism. In both investigated SNP polymorphism, the state of genetic equilibrium was maintained in Polish HF bulls. Overall, the obtained results identified four haplotypes with the highest frequencies of CG (0.493%) and TA (0.476%) haplotypes, and the lowest frequencies of CA (0.02%) and TG (0.01%) haplotypes, respectively.Conclusions: Study concludes that both polymorphism could be further investigated for the trait-associated studies in the breeding population of Polish HF cattle.