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Polymorphisms of endothelial nitric oxide synthases (eNOS) have been associated with cancer susceptibility. Also, metabolic syndrome is associated with cancer malignancy. However, the effect of eNOS polymorphisms and metabolic syndrome on colorectal cancer (CRC) prognosis remains unclear.To investigated whether three genetic polymorphisms (- 786 T C rs2070744, 4a4b rs869109213, and 894G T rs1799983) in the eNOS and metabolic syndrome (MetS) were associated with CRC patient survival.We genotyped three polymorphisms of eNOS (- 786 T C, 4a4b, and 894G T) in 312 CRC cases from the Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Although the three eNOS polymorphisms were not causative of MetS, the TT genotype of the 894G T polymorphism was associated with a worse survival rate compared with the GG genotype in the CRC group with MetS than in the CRC group without MetS (5-years survival; adjusted HR = 54.777; 95% CI 5.073-591.487 and RFS; adjusted HR = 14.909; 95% CI 1.571-141.528).The eNOS polymorphisms were not associated with metabolic syndrome prevalence in CRC patients. However, our findings suggest that the eNOS 894G T polymorphism with MetS was associated with poor clinical outcomes.

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G was carried out by TaqMan miRNA RT-Real Time polymerase chain reaction (PCR). Four polymorphisms were identified, including miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G. MiR-10a dominant model (AA vs. AT + TT) and miR-499bGG genotypes were associated with increased RPL risk (adjusted odds ratio [AOR] = 1.520, 95% confidence interval [CI] = 1.038–2.227, p = 0.032; AOR = 2.956, 95% CI = 1.168–7.482, p = 0.022, respectively). Additionally, both miR-499 dominant (AA vs. AG + GG) and recessive (AA + AG vs. GG) models were significantly associated with increased RPL risk (AOR = 1.465, 95% CI = 1.062–2.020, p = 0.020; AOR = 2.677, 95% CI = 1.066–6.725, p = 0.036, respectively). We further propose that miR-10aA>T, miR-30cA>G, and miR-499bA>G polymorphisms effects could contribute to RPL and should be considered during RPL patient evaluation.

Large artery disease (LAD), cardioembolism (CE), and small vessel disease (SVD) are well-established causes of ischemic stroke. Although a founder variant of RNF213 has been regarded a genetic susceptibility for Moyamoya disease (MMD) and certain types of intracranial atherosclerotic stenosis (ICAS), correlations between RNF213 variants and ischemic stroke with SVD remain largely unknown. This study aimed to characterize the associations of four RNF213 polymorphisms (4448G>A, 4810G>A, 4863G>A, and 4950G>A) with ischemic stroke subtypes in Koreans. Genetic data from 529 stroke patients were analyzed and compared to 424 age- and sex-matched controls. Genetic variants of RNF213, as obtained from the Human Gene Mutation Database, were analyzed in the study subjects using the polymerase chain reaction restriction fragment length polymorphism assay. We investigated four single-nucleotide polymorphisms of RNF213 to elucidate their association with ischemic stroke [LAD, (n = 192), SVD (n = 145) and CE (n = 51)]. The RNF213 4950G>A genotype was observed more frequently in cerebral stroke patients and was more strongly associated with SVD than LAD (P = 0.014). RNF213 4448/4950 in combination with G–A was higher in SVD patients. However, the RNF213 4863/4950 allele combination was associated with increased risk of SVD and LAD. These results confirmed that RNF213 4950GA+AA variants were more frequent in ischemic stroke, especially in SVD, and that RNF213 G–G–G–A and G–G–G–A (4448/4810/4863/4950) haplotype sequences play a role in LAD and CE as well as SVD. Our data reported that the RNF213 4950G>A genotypes and several RNF213 (4448/4810/4863/4950) haplotypes were associated with ischemic stroke in Koreans.

We investigated the association between the Hox transcript antisense RNA (HOTAIR) polymorphisms rs4759314, rs920778, rs1899663, and rs7958904 and primary ovarian insufficiency (POI) in Korean women.We conducted a case-control study of 134 Korean women with POI and 383 control individuals with at least one live birth and no history of pregnancy loss.The GT genotype of rs1899663 was associated with a decreased risk of POI compared with other genotypes at that locus. In addition, compared with the wild-type homozygous genotypes, the combination of the AA genotype of rs4759314 and the GC genotype of rs7958904 was associated with a decreased risk of POI (P 0.05), whereas the combination of the GG genotype of rs1899663 and the GC genotype of rs7958904 was associated with an increased risk of POI (P = 0.003). Haplotype analysis revealed that certain haplotypes involving some or all of the polymorphisms were associated with a decreased risk of POI, whereas other haplotypes were associated with an increased risk of POI. Serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol differed between patients with POI and control individuals (P 0.05).Our results suggest that the HOTAIR polymorphisms rs4759314, rs920778, rs1899663, and rs7958904 are involved in POI.

Recurrent pregnancy loss (RPL) is the loss of two or more consecutive pregnancies before 20 weeks of gestational age. Our study investigated whether mucin 4 (MUC4) polymorphisms are associated with RPL. MUC polymorphisms (rs882605 C>A, rs1104760 A>G, rs2688513 A>G, rs2258447 C>T, and rs2291652 A>G) were genotyped in 374 women with RPL and 239 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis and the TaqMan probe SNP genotyping assay. Differences in genotype frequencies between cases of RPL and the controls were compared. MUC4 rs882605 C>A and rs1104760 A>G polymorphisms were associated with increased incidence of RPL in three and four or more pregnancy loss patients. The haplotype analyses showed a tendency for the allelic effect including the association of MUC4 rs882605 A and rs1104760 G alleles with increased incidence of RPL. In addition, the MUC4 rs882605 CA/MUC4 rs2258447 CC genotype combination was associated with increased RPL prevalence. The two exonic polymorphisms lead to amino acid changes of protein and may act as pathogenic variants for RPL. In conclusion, the MUC4 rs882605 C>A and MUC4 rs1104760 A>G polymorphisms were associated with the susceptibility of RPL and we considered them as potential biomarkers for RPL.

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in

Coronary artery disease (CAD), a leading cause of death worldwide, has a complex etiology comprising both traditional risk factors (type 2 diabetes, dyslipidemia, arterial hypertension, and cigarette smoking) and genetic factors. Vascular endothelial growth factor (VEGF) notably contributes to angiogenesis and endothelial homeostasis. However, little is known about the relationship between CAD and VEGF polymorphisms in Koreans. The aim of this study is to investigate the associations of 2 VEGF promoter region polymorphisms (−1154G>A [rs1570360], −1498T>C [rs833061]) and 4 VEGF 3′-UTR polymorphisms (+936C>T [rs3025039], +1451C>T [rs3025040], +1612G>A [rs10434], and +1725G>A [rs3025053]) with CAD susceptibility in Koreans. We studied 885 subjects: 463 CAD patients and 422 controls. Genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism analysis and TaqMan allelic discrimination assays, and the genotype frequencies were calculated. We then performed haplotype and genotype combination analyses and measured the associations between VEGF polymorphisms and clinical variables in both the CAD patients and control subjects. We detected statistically significant associations between CAD and certain VEGF allele combinations. In the haplotypes of 5 single-nucleotide polymorphisms, the VEGF allele combination −1154A/+936T was associated with a decreased prevalence of CAD (A-T-T-G-G of VEGF −1154G>A/−1498T>C/+936C>T/+1612G>A/+1725G>A, AOR = 0.077, p = 0.021). In contrast, the VEGF allele combinations −1498T/+1725A and −1498T/+1612A/+1725A were associated with an increased prevalence of CAD (G-T-C-C-A of VEGF −1154G>A/−1498T>C/+936C>T/+1451C>T/+1725G>A, AOR = 1.602, p = 0.047; T-C-C-A-A of VEGF −1498T>C/+936C>T/+1451C>T/+1612G>A/+1725G>A, AOR = 1.582, p = 0.045). Gene–environment combinatorial analysis showed that the combination of the VEGF +1725AA genotype and several clinical factors (e.g., body mass index, hemoglobin A1c, and low-density lipoprotein cholesterol) increased the risk of CAD. Therefore, we suggest that VEGF polymorphisms and clinical factors may impact CAD prevalence.

Recurrent implantation failure (RIF) is defined when pregnancy failure occurs after two consecutive in vitro fertilization-embryo transfers to the endometrium using at least four high-quality embryos in women. MicroRNAs are well-known function modulators and are involved in many diseases. Recently, studies on microRNA and recurrent pregnancy loss (RPL) have been actively carried out; however, single nucleotide polymorphisms of miRNA in RPL are not well known. Therefore, we set the aim of this study to identify whether polymorphisms in miRNAs that miR-27aA>G, miR-423C>A, miR-449bA>G, and miR-604A>G are risk factors for idiopathic recurrent implantation failure (RIF) in Korean women. Genotyping was assessed with a polymerase chain reaction–restriction fragment length polymorphism assay. We examined polymorphisms in four miRNA genes: miR-27aA>G, miR-423C>A, miR-449bA>G, and miR-604A>G. We found that the miR-27aA>G, miR-449bA>G, and miR-604A>G polymorphisms were significantly associated with a risk of RIF. In addition, the miR-27aA>G and miR-449bA>G polymorphisms were associated with the frequency of implantation failures. Specifically, the miR-449bAG+GG genotype was associated with RIF prevalence (total RIF: adjusted odd ratio [AOR] = 1.584, 95% CI = 1.008–2.490, P = 0.046; IF ≥ 3 group: AOR = 1.747, 95% CI = 1.088–2.803, P = 0.021; IF ≥ 4: AOR = 1.932, 95% CI = 1.122–3.327, P = 0.018). Based on these results, the miR-449b A>G may be a predisposing factor to RIF susceptibility. However, the mechanism underlying the function of miR-449b A>G in RIF remains to be determined and further studies are needed to improve understanding of the roles of miR-449b A>G, using a larger and more heterogeneous cohort.

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3′-UTR polymorphisms, 1100T&gt, C [rs699517] and 1170A&gt, G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A&gt, G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.

Research question Are single nucleotide polymorphisms of microRNAs (miRNAs) and risk of idiopathic recurrent pregnancy loss (RPL) associated? Design A total 375 patients with idiopathic RPL (age, mean ± standard deviation [SD] 33.02 ± 4.24 years; body mass index [BMI], mean ± SD, 21.57 ± 3.70 kg/m2) and 276 control participants (age, mean ± SD, 33.01 ± 5.27 years; BMI, mean ± SD, 21.58 ± 3.20) were recruited. Pregnancy loss was diagnosed using human chorionic gonadotrophin concentrations, ultrasonography and/or physical examination prior to 20 weeks of gestation. The genotype of the participants was determined by polymerase chain reaction restriction fragment length polymorphism analysis. Statistical analysis was performed to investigate the differences in frequencies between the control and RPL genotypes Results The miR-150G>A heterozygous genotype was significantly associated with increased risk of RPL (adjusted odds ratio 2.502, 95% confidence interval 1.555–4.025; P = 0.0002). The miR-1179A>T heterozygous genotype was significantly associated with decreased risk of RPL (adjusted odds ratio 0.633, 95% confidence interval 0.454–0.884; P = 0.007). Some allele combinations that included miR-150A or miRNA-1179T resulted in an increase or decrease in risk of RPL, respectively. Conclusions The miR-150G>A and miR-1179A>T polymorphisms were more frequently associated with RPL compared with controls.

Cyclooxygenase-2 (COX2) plays a role in the formation of prostaglandins, which contribute to the inflammation involved in atherosclerosis. However, the role of the COX2 −765G>C polymorphism in susceptibility to coronary artery disease (CAD) is controversial. To identify the association between COX2 −765G>C polymorphism with CAD risk in Korean patients. We recruited 622 patients who were diagnosed to have coronary artery disease and 202 controls who did not have history and vascular disease risk factors. Using polymerase chain reaction-restriction fragment length polymorphism, the COX2 −765G>C polymorphism was analyzed in 622 Korean patients who received percutaneous coronary intervention and in 202 healthy control subjects. The GC+CC genotype frequencies of the −765G>C polymorphism were significantly different between the CAD and control groups. The COX2 −765G>C polymorphism showed peculiar associations with CAD according to the presence of hyperlipidemia and plasma folate levels. However, there were no associations between the −765G>C polymorphism and the rates of hypertension, diabetes mellitus, or homocysteine levels. This study suggests that the COX2 −765G>C polymorphism is a possible genetic determinant for the risk of CAD, and an individual risk factor in Koreans. Thus, further association studies between the COX2 polymorphism and atherosclerotic-related diseases such as cerebrovascular or cardiovascular diseases in other races or ethnicities will be needed.

Background Until now, an association between tissue inhibitor of metalloproteinase (TIMP) polymorphisms and primary ovarian insufficiency (POI) has not been identified. The aim of our study was to investigate whether the TIMP polymorphisms TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724), which regulate matrix metalloproteinases (MMPs), confer a risk for primary ovarian insufficiency (POI) in Korean women (further studies would be required to evaluate the associations between TIMP polymorphisms and POI in other populations). Methods We genotyped 137 POI patients and 236 controls for the single nucleotide polymorphism sites using PCR–RFLP analysis. Differences in the frequencies of the TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) genotypes between patients and controls were compared, and odds ratios and 95% confidence intervals were determined to measure of the strength of the association between the genotypes and POI. Results The TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) genotypes, but especially the TIMP2 genotypes, were found more frequently in POI patients than in control subjects. Among the four TIMP loci, the TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) haplotypes were identified more frequently in POI patients than in control subjects and conferred susceptibility to POI (P Conclusions The TIMP2G > C (rs8179090) and G > A (rs2277698) alleles were strongly associated with POI. Our data suggest that the minor TIMP2 alleles may increase POI risk in Korean women.

Thymidylate synthase (TS) is a key gene involved in the repair of DNA damage and DNA synthesis that plays an important role in vascular development and recovery. In particular, TS gene polymorphisms play a major role in the progression of vascular disease and cancer metastasis. Therefore, the aim of this study was to investigate the association of three TS polymorphisms (1100T&gt, C [rs699517], 1170A&gt, G [rs2790], and 1494ins/del [rs151264360]) with ischemic stroke and silent brain infarction (SBI) in Koreans. A total of 1299 participants (507 stroke patients, 383 SBI patients, and 409 controls) were enrolled in the study. Genotyping of the three TS polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To examine the association between TS gene polymorphisms and the diseases, we performed statistical analyses, including multivariable logistic regression and Fisher’s exact tests. We found that TS 1100T&gt, C and 1170A&gt, G genotypes were strongly associated with ischemic stroke and SBI susceptibility. More specifically, the TS 1100T &gt, C polymorphism was associated with the likelihood of ischemic stroke (TT vs. CC: AOR = 2.151, 95% CI = 1.275–3.628, P = 0.004) and SBI (TT vs. TC+CC: AOR = 1.443, 95 % CI = 1.009–2.063, P = 0.045). In contrast, the TS 1170A &gt, G polymorphism exhibited lower correlation with the risk of stroke (AA vs. GG: AOR = 0.284, 95% CI = 0.151–0.537, P &lt, 0.0001) and SBI (AA vs. GG: AOR = 0.070, 95% CI = 0.016–0.298, P = 0.0002). Furthermore, we confirmed that the TS 1100T &gt, C polymorphism was synergistic with low folic acid levels (AOR = 6.749, P &lt, 0.0001). Altogether, these results suggest that TS 1100T &gt, C and 1170A &gt, G polymorphisms are associated with the risk of ischemic stroke and SBI, and our study provides the first evidence that 3′-UTR variants in TS are potential biomarkers in ischemic stroke and SBI.

The most common type of cardiovascular disease is coronary artery disease (CAD), in which a plaque builds up inside the coronary arteries that can lead to a complete blockage of blood flow to the heart, resulting in a heart attack. The CAD may be affected by various factors including age, gender, and lipoprotein disposition as well as genetic factors and metabolic syndrome. In this study, we investigated whether three PAI-1 polymorphisms (-844 G&gt, A, -675 4G&gt, 5G, and +43 G&gt, A) and CAD-related clinical parameters are associated with CAD susceptibility. Genotyping of 463 CAD patients and 401 controls was performed using polymerase chain reaction restriction fragment length polymorphism analysis. We report that the 4G5G genotype (crude odds ratio(COR), 1.392, 95% confidence interval (CI), 1.036&ndash, 1.871, p = 0.028) and dominant model (4G4G vs. 4G5G + 5G5G, COR, 1.401, 95% CI, 1.060&ndash, 1.850, p = 0.018, adjust odds ratio, 1.371, 95% CI, 1.027&ndash, 1.831, p = 0.032) of PAI-1 -675 polymorphisms were associated with increased CAD risk. Haplotype and genotype combinations of PAI-1 -675 and +43 polymorphisms show an increased risk of CAD according to alterations of the -675 polymorphism allele or genotype. Moreover, the PAI-1 -675 polymorphisms show a synergistic effect with the metabolic syndrome component of CAD risk. This study suggests that polymorphisms in the PAI-1 genes along with the metabolic syndrome component of CAD can be useful biomarkers for CAD diagnosis and treatment.

Background Premature ovarian failure (POF) is a highly heterogeneous disorder that occurs in 1% of women of reproductive age. Very few causative genes and variants contributing to POF have been detected, and the disease remains incompletely understood. In this study, we used whole exome sequencing (WES) to identify potential causal variants leading to POF. Methods WES was conducted to identify variants in 34 Korean patients with POF, alongside 10 normal controls. Detected variants were filtered using a range of characterized bioinformatics analyses, and the machine learning tools, CADD and VEST, were used to predict pathogenic variants that could cause disease. VarSome was used for a comprehensive interpretation of the variants. Potential causal variants finally screened by these analyses were confirmed using Sanger sequencing. Results We identified nine potential causative variants in genes previously associated with POF in 8 of 34 (24%) Korean patients by WES variant analysis. These potentially pathogenic variants included mutations in the MCM8, MCM9, and HFM1 genes, which are involved in homologous recombination, DNA repair, and meiosis, and are established as causing POF. Using a combination of CADD and VEST, 72 coding variants were also identified in 72 genes, including ADAMTSL1 and FER1L6, which have plausible functional links to POF. Conclusions WES is a useful tool to detect genetic variants that cause POF. Accumulation and systematic management of data from a number of WES studies in specialized groups of patients with POF (family data, severe case populations) are needed to better comprehend the genetic landscape underlying POF.

The authors wish to make a correction to the published version of their paper [...]

This paper investigates whether glycoprotein 6 (GP6) gene polymorphisms are a risk factor for recurrent pregnancy loss (RPL) in Korean women. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction amplification. We identified five polymorphisms in the GP6 gene: rs1654410 T&gt, C, rs1671153 T&gt, G, rs1654419 G&gt, A, rs12610286 A&gt, G, and rs1654431 G&gt, A. GP6 rs1654410 CC was associated with decreased RPL risk (adjusted odds ratio = 0.292, 95% confidence interval = 0.105&ndash, 0.815, p = 0.019), and recessive genotypes were also significantly associated with decreased RPL risk (adjusted odds ratio = 0.348, 95% confidence interval = 0.128&minus, 0.944, p = 0.038). GP6 rs1654419 GA was associated with decreased RPL risk (adjusted odds ratio = 0.607, 95% confidence interval = 0.375-0.982, p = 0.042), and dominant genotypes were significantly associated with decreased RPL risk (adjusted odds ratio = 0.563, 95% confidence interval = 0.358&minus, 0.885, p = 0.013). Altogether, the genotype frequencies of GP6 rs1654410 T&gt, C and GP6 rs1654419 G&gt, A were significantly different between RPL patients and control participants. Therefore, although GP6 polymorphisms may be useful as biomarkers of RPL, additional studies with heterogeneous cohorts are required to better understand the influence of GP6 and assess its performance as a biomarker.

As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3&rsquo, untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426 C&gt, T, TCN2 rs10418 C&gt, T, SLC19A1 rs1051296 G&gt, T, and SLC19A2 rs16862199 C&gt, T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019, 95% CI, 1.533&ndash, 16.430, p &lt, 0.05) and OVCF (AOR, 5.760, 95% CI, 1.480&ndash, 22.417, p &lt, 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244, 95% CI, 1.478&ndash, 7.120, p &lt, 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287, 95% CI, 1.094&ndash, 4.782, p &lt, 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3&acute, UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.

The aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gene polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113–2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119–2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518–4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.

Recurrent pregnancy loss (RPL), which is defined as two pregnancy losses that occur before 20 weeks of gestation, is relatively common, occurring in approximately 1−5% of women. The underlying cause is often unclear, although numerous factors may contribute to RPL, including environmental and immunological factors, blood coagulation disorders, and genetics. In particular, single nucleotide variants have been associated with RPL, including those found in microRNAs (miRNAs). We investigated the association between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125aC>T, and miR-222G>T, and RPL in a cohort consisting of 361 RPL patients and 272 controls. Subjects were genotyped at miRNA loci by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and genotype frequencies were calculated. We then performed allele and genotype combination analyses and measured the association between miRNA polymorphisms and clinical variables in both RPL patients and controls. We detected a statistically significant association between RPL and the miR-25T/miR-32C/miR-125aT/miR-222T allele combination (adjusted odds ratio (AOR), 4.361; 95% confidence interval (CI), 1.496−12.72; P=0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254−7.588; P=0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183−7.257; P=0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084−5.386; P=0.026) were also associated with RPL. Analysis of variance (ANOVA) revealed that platelet counts and blood urea nitrogen levels were significantly different in RPL patients expressing different miR-125aC>T and miR-25T>C genotypes, respectively (PC and miR-32C>A. We investigated miRNAs (miR-25, miR-32, miR-125a, miR-222) in RPL patients and healthy controls. Significantly different allele frequencies were detected by ANOVA. We suggest that miRNAs and clinical factors can impact RPL occurrence.

Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke. Recent studies have suggested that variants of RNF213, a susceptibility gene for moyamoya disease (MMD), are also related to non-MMD ICASO. Regarding the predominant involvement of steno-occlusion on anterior circulation in MMD, we hypothesized that the ICASO distribution pattern (anterior/posterior) in non-MMD may differ according to RNF213 variants. This study analyzed 1024 consecutive Korean subjects without MMD who underwent computed tomography angiography (CTA) or magnetic resonance angiography (MRA). We evaluated four single nucleotide polymorphisms (SNPs) in the exon region of RNF213: 4448G &gt, A (rs148731719), 4810G &gt, A (rs112735431), 4863G &gt, A (rs760732823), and 4950G &gt, A (rs371441113). Associations between RNF213 variants and anterior/posterior ICASO were examined using multivariate logistic regression analysis. Anterior ICASO was present in 23.0% of study subjects, and posterior ICASO was present in 8.2%. The GA genotype of RNF213 4810G &gt, A (adjusted odds ratio (AOR) [95% confidence interval (CI)], 2.39 [1.14&ndash, 4.87] compared to GG, p = 0.018) and GA genotype of RNF213 4950G &gt, A (AOR [95% CI], 1.71 [1.11&ndash, 2.63] compared to GG, p = 0.015) were more frequent in subjects with anterior ICASO. The genotype frequency of RNF213 4863G &gt, A differed significantly according to the presence of posterior ICASO. Further investigations of the functional and biological roles of RNF213 will improve our understanding of the pathomechanisms of ICASO and cerebrovascular disease.

In colorectal carcinogenesis, the unique molecular and genetic changes that occur within cells result in specific CRC phenotypes. The involvement of the long non-coding RNA, HOTAIR, in cancer development, progression, and metastasis is well-established. Various studies have reported on the contribution of HOTAIR to cancer pathogenesis. Therefore, we selected four HOTAIR polymorphisms (rs7958904G>C, rs1899663G>T, rs4759314A>G, and rs920778T>C) to evaluate the association of each variant with CRC prevalence and prognosis. We conducted a case–control study of 850 individuals to identify the genotype frequencies of each polymorphism. The study population included 450 CRC patients and 400 control individuals that were randomly selected following a health screening. Notably, rs7958904 and rs1899663, their hetero genotype, and the dominant model were significantly different when compared to the healthy control group (rs7958904; AOR = 1.392, 95% CI = 1.052–1.843, P = 0.021). To evaluate the effect of HOTAIR polymorphisms on the survival rate, we analyzed patient mortality and relapse occurrence within 3 and 5 years with Cox-regression analysis. The rs7958904 CC polymorphism mortality rate was significantly higher than the GG polymorphism mortality rate (adjusted HR = 2.995, 95% CI = 1.189–7.542, P = 0.021). In addition, the rs920778 CC genotype was significantly different than the TT genotype (adjusted HR = 3.639, 95% CI = 1.435–9.230, P = 0.007). In addition, this study confirmed that genetic variants of HOTAIR alter the mRNA expression level (P < 0.01). We suggest that HOTAIR rs7958904G>C which is associated with CRC prevalence and mortality is a potential biomarker for CRC. The association between HOTAIR gene polymorphisms and CRC prevalence were reported for the first time.

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation, and the incidence of RPL is estimated at 1% of all pregnancies. While the etiologies of RPL are diverse, immune function is considered to be an important cause of RPL. In particular, the complement system is essential for stable development of the placenta and fetus. Moreover, complement factor D (CFD) and complement factor H (CFH) are important regulators of the complement system and are associated with diseases, such as age-related macular degeneration. Therefore, we investigated whether polymorphisms of CFD and CFH are associated with RPL in 412 women with RPL and 384 control women. Genotyping of three polymorphisms (CFD rs2230216, CFH rs1065489, and CFH rs1061170) was performed by TaqMan probe real-time PCR and PCR-restriction fragment length polymorphism. Association of three polymorphisms with RPL was evaluated by statistical analysis. The GT/TC genotype combination of CFH rs1065489 G&gt, T/CFH rs1061170 T&gt, C was associated with a decreased risk of RPL occurrence compared with reference genotypes (adjusted odds ratio [AOR] = 0.439, 95% confidence interval [CI] = 0.238&ndash, 0.810, p = 0.008), and this association remained significant after adjustment for multiple comparisons using false discovery rate (FDR) correction (p = 0.040). In addition, the CFH rs1065489G&gt, T polymorphism is associated with homocysteine and prolactin level and CFH rs1061170 TC genotype is related to uric acid and triglycerides level in RPL patients. Therefore, those factors could be possible clinical risk factors in RPL patients.

Biotransformation of lignocellulose by microbial fermentation is usually preceded by thermo-chemical pretreatments followed by enzymatic hydrolysis of cellulose. Derivatives formed during the pretreatment of the lignocellulosic biomass inhibit enzymatic hydrolysis as well as microbial fermentation. Pretreated lignocellulose hydrolysate contains many derivatives of either furanic or phenolic inhibitory derivatives. In the present study, laccase was used to detoxify three different types of lignocellulosic derivatives that are highly toxic to microbial fermentation due to their low hydrophilic nature, namely furfural, acetosyringone, and coniferyl aldehyde. A minimal inhibitory concentration (MIC) test was carried out with Saccharomyces cerevisiae . The MIC of furfural, acetosyringone, and coniferyl aldehyde was 12 mM, 24 mM, and 1.5 mM, respectively. Laccase was immobilized on to cellulose nanofiber produced by Gluconacetobacter xylinus . Immobilized laccase showed a better pH and thermal stability than free laccase. Reuse of immobilized laccase retains 85% of its enzyme activity after 16 recycles. Immobilized laccase completely degraded the three lignocellulose inhibitory derivatives after 36 h of incubation at 40 °C. Finally, the degradation was confirmed by ultraviolet visible spectroscopy (UV–VIS spectrum), high performance liquid chromatography and liquid chromatography mass spectrometry. Interestingly, it was found that the effect of enzymatic degradation depends on the structural variation of the lignocellulosic derivatives as laccase alone detoxified the furfural and coniferyl aldehyde, whereas a redox mediator HOBt was needed for the detoxification of ketone based lignin derivative acetosyringone.

In colorectal carcinogenesis, the unique molecular and genetic changes that occur within cells result in specific CRC phenotypes. The involvement of the long non-coding RNA, HOTAIR, in cancer development, progression, and metastasis is well-established. Various studies have reported on the contribution of HOTAIR to cancer pathogenesis. Therefore, we selected four HOTAIR polymorphisms (rs7958904G>C, rs1899663G>T, rs4759314A>G, and rs920778T>C) to evaluate the association of each variant with CRC prevalence and prognosis. We conducted a case–control study of 850 individuals to identify the genotype frequencies of each polymorphism. The study population included 450 CRC patients and 400 control individuals that were randomly selected following a health screening. Notably, rs7958904 and rs1899663, their hetero genotype, and the dominant model were significantly different when compared to the healthy control group (rs7958904; AOR = 1.392, 95% CI = 1.052–1.843, P = 0.021). To evaluate the effect of HOTAIR polymorphisms on the survival rate, we analyzed patient mortality and relapse occurrence within 3 and 5 years with Cox-regression analysis. The rs7958904 CC polymorphism mortality rate was significantly higher than the GG polymorphism mortality rate (adjusted HR = 2.995, 95% CI = 1.189–7.542, P = 0.021). In addition, the rs920778 CC genotype was significantly different than the TT genotype (adjusted HR = 3.639, 95% CI = 1.435–9.230, P = 0.007). In addition, this study confirmed that genetic variants of HOTAIR alter the mRNA expression level (P < 0.01). We suggest that HOTAIR rs7958904G>C which is associated with CRC prevalence and mortality is a potential biomarker for CRC. The association between HOTAIR gene polymorphisms and CRC prevalence were reported for the first time.

Silent brain infarction (SBI) is a cerebral infarction identified through brain imaging. In particular, studies have shown that the presence of SBI in elderly patients increases their risk of cognitive dysfunction, impairment and dementia. However, little research has been published on the relevance of SBI to these risks for the Korean population. The association between potassium voltage‑gated channel subfamily Q member 2 (KCNQ2), transcription factor 4 (TCF4) and regulator of G‑protein signaling 18 (RGS18) genotypes and SBI were investigated using whole‑exome sequencing and PCR restriction fragment length polymorphism (RFLP) analysis. The study population included 407 patients with SBI (171 males) and 401 control subjects (172 males). Genotyping was performed using PCR RFLP. Interestingly, TCF4 rs9957668T>C polymorphisms were associated with SBI prevalence [TT vs. CC: adjusted odds ratio (AOR), 1.815, 95% confidence intervals (CI), 1.202‑2.740; TT vs. TC+CC: AOR, 1.492, 95% CI, 1.066‑2.088; TT+TC vs. CC: AOR, 1.454, 95% CI, 1.045‑2.203]. The combination of KCNQ2 rs73146513A>G and TCF4 rs9957668T>C genotypes was associated with increasing SBI prevalence (AG/CC: AOR, 3.719, 95% CI, 1.766‑7.833; AA/CC: AOR, 3.201, 95% CI, 1.387‑7.387). The present study showed that TCF4 rs9957668T>C polymorphisms may be risk factors for SBI. Therefore, the TCF4 rs9957668T>C polymorphism may serve as a biomarker for increased risk of SBI in the Korean population.

Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A &gt, G, DROSHA rs10719T &gt, C, RAN rs14035C &gt, T and XPO5 rs11077A &gt, C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018, XPO5 rs11077AA + AC versus CC: p &lt, 0.001). Analysis of allele combinations of all four polymorphisms (DICER1, DROSHA, RAN, XPO5) revealed that A-T-T-A was associated with decreased VTE prevalence (p = 0.0002), and A-T-C-C was associated with increased VTE prevalence (p = 0.027). Moreover, in subjects with provoked VTE, the DROSHA rs10719T &gt, C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p &lt, 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects.

Numerous studies have examined the genetic association of vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) with recurrent pregnancy loss (RPL). However, of the four known SNPs in the 3&prime, untranslated region (3&prime, UTR) of VEGF, three SNPs&mdash, namely rs3025040 (1451C&gt, T), rs10434 (1612G&gt, A), and rs3025053 (1725G&gt, A)&mdash, remain poorly characterized with regard to RPL. Herein, we evaluated the association between these three SNPs in the VEGF 3&prime, UTR and RPL susceptibility. We analyzed VEGF 3&prime, UTR gene variants in with and without RPL using TaqMan allelic discrimination. There were significant differences in the genotype frequencies of 1612G&gt, A (GA: adjusted odds ratio (AOR), 0.652, 95% confidence interval (CI), 0.447&ndash, 0.951, p = 0.026) and 1725G&gt, A (GA: AOR, 0.503, 95% CI, 0.229&ndash, 0.848, p = 0.010) in RPL patients vs. controls. Our results indicate that the 1612G&gt, A and 1725G&gt, A polymorphisms in the 3&prime, UTR of VEGF are associated with RPL susceptibility in Korean women. These data suggest that VEGF 3&prime, UTR polymorphisms may be utilized as biomarkers for the detection of RPL risk and prevention.

PURPOSE: Vitamin B12 (cobalamin, Cbl) plays a role in the recycling of folate, which is important in pregnancy. Transcobalamin II (TCN2) and transcobalamin receptor (TCblR) proteins are involved in the cellular uptake of Cbl. TCN2 binds Cbl in the plasma, and TCblR binds TCN2-Cbl at the cell surface. Therefore, we investigated the potential association between polymorphisms in Cbl transport proteins, TCN2 and TCblR, and recurrent implantation failure (RIF) susceptibility. METHODS: The genotypes of TCN2 67A>G, TCN2 776C>G, and TCblR 1104C>T were determined for RIF patients and healthy controls using a polymerase chain reaction restriction fragment length polymorphism assay. Additionally, statistical analysis was performed to compare the genotype frequencies between RIF patients and controls. RESULTS: The TCN2 67 polymorphism AG type was associated with RIF risk. Some allele combinations that contained the TCN2 67 polymorphism G allele were associated with increased RIF risk, whereas other allele combinations that contained the TCblR 1104 polymorphism T alleles were associated with decreased RIF risk. In genotype combination analysis, two combinations containing the TCN2 67 polymorphism AG type were associated with RIF risk. CONCLUSION: Our study showed that the polymorphisms of TCN2 and TCblR are associated with RIF and are potential genetic predisposing factors for RIF among Korean women. Additionally, our findings support a potential role for TCN2 and TCblR in RIF among Korean women. However, further studies are required to investigate the role of the polymorphisms in those proteins and RIF because the roles of the TCN2 and TCblR polymorphisms in RIF are not clear. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01455-4) contains supplementary material, which is available to authorized users.

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction−restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257−0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483−0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

Background Recent studies have extensively investigated the role of miRNAs in colorectal cancer (CRC), and several associations have been reported. In addition, single nucleotide polymorphisms (SNPs) in promoter regions of miRNAs have been shown to affect miRNA expression. Therefore, we aimed to analyze the effect of miRNA polymorphisms on CRC susceptibility. Methods We conducted association studies on the relationships between the miRNA polymorphisms miR-130bT > C rs373001, miR-200bT > C rs7549819, and miR-495A > C rs2281611 and CRC with 472 CRC patients and 399 control subjects in Korea. Results Multivariate logistic regressions of the CRC subgroups showed that the miR-495CC genotype associated with rectal cancer (AA+AC vs. CC; adjusted odds ratio (AOR) for CC, 1.592; 95% confidence interval (CI), 1.071–2.368; P = 0.022). The gene-environment combinatorial analysis showed that the combination of miR-495A > C and low plasma folate contributed to an increased risk of rectal cancer (AA+AC vs. CC; AOR for CC, 3.829; 95% CI, 1.577–9.300; P = 0.003). In the survival analysis, miR-200bT > C associated with CRC patient mortality (TT vs TC + CC; adjusted hazard ratio for TC + CC, 0.592; 95% CI, 0.373–0.940; P = 0.026). Conclusion In this study, we found that miR-200b and miR-495 polymorphisms are involved in CRC susceptibility and prognosis. Electronic supplementary material The online version of this article (10.1186/s12885-019-5641-1) contains supplementary material, which is available to authorized users.

Colorectal cancer (CRC) is one of the most common types of cancers, as evidenced by the >1.2 million patient diagnoses and 600,000 mortalities globally each year. Recently, the microRNA (miR/miRNA)-34 miRNA precursor family was revealed to participate in the tumor protein (TP)-53 pathway, which is frequently involved in CRC. Furthermore, the expression of miR-34 is reportedly regulated by DNA methylation. Accordingly, the present study investigated the correlation between the methylation status of miR-34 miRNAs and miR-34 expression in paired CRC tumor and normal tissues. The methylation status of miR-34a and miR-34b/c was determined using the MethyLight assay, and the expression of miR-34a and miR-34b/c in the same paired tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. The results revealed significantly elevated miR-34a (P=0.012) and miR-34b/c (P

A recent study of the ischemic stroke described the roles played by miRNAs in the downregulation of specific cell-cycle gene expression and it is thought to require the development of biomarkers for the prognostic of ischemic stroke. Here, we hypothesized that four miRNA polymorphisms (miR-10a, miR-27a, miR-34b/c, and miR-300) may affect stroke susceptibility and mortality. Blood samples were collected from 530 patients and 403 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and real-time PCR. We found that the miR-300 rs12894467 TC genotype and the dominant model (AOR: 2.069, p-value: 0.017, AOR: 1.931, p-value: 0.027) were significantly associated with an increased risk for the ischemic stroke subtype. In Cox proportional hazard regression models, the miR-10a rs3809783 A&gt, T and miR-34b/c rs4938723 T&gt, C polymorphisms were associated with the mortality rates among ischemic stroke patients. We found that a miR-300 polymorphism was associated with increased ischemic stroke susceptibility among the Korean population. Additionally, polymorphisms in miR-10a and miR-34b/c were associated with the increased or decreased mortality of ischemic stroke patients. This study marks the first report of an association between ischemic stroke and miRNA polymorphisms (miR-10aA&gt, T, miR-27aT&gt, C, miR-34b/cT&gt, C, and miR-300T&gt, C) in the Korean population.

Recurrent implantation failure (RIF) is defined when pregnancy failure occurs after two consecutive in vitro fertilization-embryo transfers to the endometrium using at least four high-quality embryos in women. MicroRNAs are well-known function modulators and are involved in many diseases. Recently, studies on microRNA and recurrent pregnancy loss (RPL) have been actively carried out; however, single nucleotide polymorphisms of miRNA in RPL are not well known. Therefore, we set the aim of this study to identify whether polymorphisms in miRNAs that miR-27aAG, miR-423CA, miR-449bAG, and miR-604AG are risk factors for idiopathic recurrent implantation failure (RIF) in Korean women. Genotyping was assessed with a polymerase chain reaction-restriction fragment length polymorphism assay. We examined polymorphisms in four miRNA genes: miR-27aAG, miR-423CA, miR-449bAG, and miR-604AG. We found that the miR-27aAG, miR-449bAG, and miR-604AG polymorphisms were significantly associated with a risk of RIF. In addition, the miR-27aAG and miR-449bAG polymorphisms were associated with the frequency of implantation failures. Specifically, the miR-449bAG+GG genotype was associated with RIF prevalence (total RIF: adjusted odd ratio [AOR] = 1.584, 95% CI = 1.008-2.490, P = 0.046; IF ≥ 3 group: AOR = 1.747, 95% CI = 1.088-2.803, P = 0.021; IF ≥ 4: AOR = 1.932, 95% CI = 1.122-3.327, P = 0.018). Based on these results, the miR-449b AG may be a predisposing factor to RIF susceptibility. However, the mechanism underlying the function of miR-449b AG in RIF remains to be determined and further studies are needed to improve understanding of the roles of miR-449b AG, using a larger and more heterogeneous cohort.

MicroRNAs (miRNAs/miRs) are short, non‑coding RNAs that are implicated in tumorigenesis, functioning as tumor suppressors and oncogenes. However, the clinical significance of miRNA expression profiles for brain tumors remains unclear. Therefore, the present study was designed to investigate the associations between miRNA genetic variants and brain tumor risk. A total 362 participants were recruited, including 179 who were healthy subjects and 183 who were patients with brain tumors confirmed as gliomas, meningiomas or schwannomas. This study investigated the single nucleotide polymorphisms miR‑146aC>G, miR‑149T>C, miR‑196a2T>C and miR‑499A>G by polymerase chain reaction‑restriction fragment length polymorphism. It was found that the dominant miR‑149 and CC genotypes were significantly more frequent in patients with glioma. The odds ratios for the C‑C‑C‑G, C‑T‑C‑G and G‑C‑T‑G haplotypes (miR‑146aC>G‑miR‑149T>C‑miR‑196a2T>C‑miR‑499A>G) were significantly increased in glioma, as were the odds ratios for the GCT haplotype of miR‑146aC>G, miR‑149T>C and miR‑196a2T>C, and for the C‑C‑G haplotype of miR‑149T>C, miR‑196a2T>C and miR‑499A>G. In meningioma, the odds ratios were increased in the G‑T‑C‑G haplotype of miR‑146aC>G, miR‑149T>C, miR‑196a2T>C and miR‑499A>G. The odds ratios were also increased in the G‑C‑G haplotype of miR‑146aC>G, miR‑196a2T>C and miR‑499A>G, and in the C‑C‑G haplotype of miR‑149T>C, miR‑196a2T>C and miR‑499A>G. The odds ratios for schwannoma were increased in the G‑C‑T‑G haplotype of miR‑146aC>G, miR‑149T>C, miR‑196a2T>C and miR‑499A>G, and in the C‑C‑G haplotype of miR‑149T>C, miR‑196a2T>C and miR‑499A>G. In conclusion, these results suggested that the miR‑149 polymorphism may be involved in the development of gliomas, and the C‑C‑G haplotype of miR‑149T>C, miR‑196a2T>C and miR‑499A>G showed increased odds ratios for all types of brain tumors.

Results to date suggest that microalgal Thraustochytrids family strains can be used to produce high-functional omega-3 rich oil (~ 30-70% of dry cell weight) and carotenoid-based antioxidant pigments simultaneously with value-added bioactive potential. In the present study, we describe the isolation and characterization of a new Thraustochytrid Schizochytrium sp. from the west coastal area of Korea. This newly isolated Thraustochytrid, identified as Schizochytrium sp. through 18S rRNA analysis and named SH104, simultaneously produces high levels of DHA and carotenoid-based antioxidant pigments. An improved Schizochytrium mutant, named SHG104, was obtained from the original host strain by γ-irradiation-induced mutagenesis. Under combined temperature-shift cultivation conditions employing white-light LEDs (light-emitting diodes), Schizochytrium sp. SHG104 yielded 10.8 g L-1 of biomass comprising 45.8% total lipids (32.1% DHA) and 4.6 mg L-1 of astaxanthin. In addition to DHA, the main fatty acids produced by Schizochytrium sp. SHG104 were palmitic acid and a trace of other long-chain fatty acids. The carotenoid profile of SH104 and SHG104 was β-carotene, astaxanthin, canthaxanthin, pheonicoxanthin and echinenone, which analyzed by HPLC and LC/APCI-MS. Furthermore, genomic analysis of Schizochytrium and Aurantiochytrium microalgae confirmed that the presence of carotenogenesis pathway enzymes and genes including geranylgeranyl diphosphate, phytoene synthase, lycopene cyclase, and cytochrome P450 hydroxylase that necessary for the production of antioxidants via a complete biosynthetic KEGG synthesis pathway. This newly isolated Schizochytrium microalga potentially have wide application as a source of antioxidants for astaxanthin-containing pigments, commercial omega-3 lipids and feed additives, such as nutritional supplements for aquaculture.