Single Nucleotide Polymorphisms Rs2910164 Research Articles

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

Background Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. Methods In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated. Results The rs2910164C allele (OR = 1.56, 95% CI = 1.10–2.21, p = 0.012) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, p = 0.034, respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR = 0.57, 95% CI = 0.33–0.99, p = 0.048) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, p = 0.043) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR = 0.44, 95% CI = 0.21–0.90, p = 0.024). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC. Conclusion Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

Relationship analysis of the miR-196a2 polymorphism (rs11614913) with colorectal cancer risk in southern Khorasan, eastern Iran

BackgroundIt has been considered that colorectal cancer (CRC) is the fourth most common cause of cancer death with multifactorial characteristics and genetic precedent can provide a comprehensive sight to its etiology. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs /miRs) sequence are considered as prognostic markers with high specify for CRC detection and prevention. Recent researches have indicated that rs11614913 is the most common SNP related to the vulnerability to many of the cancers. This case-control study aims to quantify the correlation between rs11614913 in miR-196a2 and CRC in southeast Iranian population. MethodsTo identify the role of rs11614913 SNP in susceptibility to CRC, this case-control study is done on CRC patients (n = 52) and healthy persons (n = 120) of the same organization with a uniform gender and age dispensation compared to CRC patients and no prior background of any kind of cancer by PCR-RFLP technique. Statistical analysis is carried out utilizing SPSS (version 16). ResultsAfter the comparison of genotype and allele distribution of this SNP among case and control groups, it has not shown any statistically significant findings (P > 0.05). ConclusionWe have not discovered statistically significant association between rs11614913 polymorphism in miR-196a2 and the risk of CRC in the southeast Iranian society.

Abstract 2470: Comprehensive functional modeling of pan-cancer risk SNP rs6983267 in human CRC cells via scarless CRISPR/Cas9 genome editing

Abstract With the continued emergence of Genome-Wide Association study-identified risk loci for complex diseases as well as a sharp increase in the number of variants of uncertain significance (VUS) identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Our lab has previously published a novel variant modeling pipeline which combines CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) technology to create scarless isogenic cell models of cancer variants in ~1 month. In this study, we utilize our pipeline to model risk Single Nucleotide Polymorphism (SNP) rs6983267 in human colorectal cancer (CRC) cells and present the first functional characterization for this risk SNP at the most precise level possible with current technology, isogenic clones of the same cell lines that only differ by a single base. Rs6983267 is located within a known Mycenhancer and has been shown to exert risk-allele specific increase in enhancer activity. However, we do not observe risk-allele specific upregulation of Mycexpression in our isogenic models. Instead, we find that presence of the risk allele confers significant effects within the cell locally, modulating activity of adjacent binding site for WNT transcription factor, TCF7L2, and a subset of genes associated with enhancer function. Through 3D interaction analysis, we identify difference in interactions incisacross the three genotypes including the loss of interaction with Mycin the heterozygous and homozygous reference lines, indicating genotype-specific changes of enhancer gene targets in CRC cells. Together, these variations lead to global effects, affecting transcriptional expression of genes involved in WNT signaling, cell-to-cell adhesion and PI3K-Akt signaling pathways. These results suggest the loss of a single risk allele in CRC cells confers a transcriptional change associated with overall decreased cancer activity despite expression of the putative target gene of the enhancer, Myc, not being significantly affected. Interestingly, engineered loss of both risk alleles in CRC cells does not further the overall effect, indicating the activation of a compensatory mechanism, possibly due to redundancy of regulatory pathways affected. Activation of such compensatory mechanisms could demonstrate an important limitation to the use of established cancer cell lines in the functional modeling of risk-associated variants, which are the current standard models in the field. Our study provides an important contribution to the current efforts of functional characterization of novel VUSs and non-coding SNPs associated with cancer risk. It will become important to consider validation standards and functional thresholds for inclusion of lower penetrance susceptibility alleles in clinical decision-making as the field continues to advance towards the ultimate goal of precision medicine in cancer. Citation Format: Nicole B. Coggins, Henriette O'Geen, David J. Segal, Luis G. Carvajal-Carmona. Comprehensive functional modeling of pan-cancer risk SNP rs6983267 in human CRC cells via scarless CRISPR/Cas9 genome editing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2470.

Association between the Wilms tumor-1 rs16754 polymorphism and acute myeloid leukemia: A MOOSE-compliant meta-analysis.

The Wilms tumor-1 (WT1) protein is an important regulator of malignant hematopoiesis and has been implicated in the pathogenesis of acute myeloid leukemia (AML). Recently special attention has been paid to the relationship of the WT1 single nucleotide polymorphism (SNP) rs16754 with AML risk and outcome, but the conflicting results made it difficult to draw definitive conclusions. In the present study, we systematically reviewed the literature and performed a meta-analysis of existing evidence. We searched Embase, Pubmed, Web of Science, Medline, Cochrane Library, Wanfang, and China National Knowledge Infrastructure databases using predefined search methodology for relevant studies. We pooled odd ratio (OR) with 95% confidence intervals (95% CI) to evaluate the association between SNP rs16754 and AML risk. In addition, we analyzed hazard ratio (HR) with 95% CI for overall survive, relapse-free survival, and disease-free survival. Q-statistic was used to assess the homogeneity and Egger test was used to evaluate publication bias. Eleven studies met the inclusion criteria for analysis. The results of fixed-effect meta-analyses revealed no association between SNP rs16754 and AML risk (AA + GA vs GG: OR = 0.92, 95% CI: 0.71–1.19, P = .518; AA vs GA + GG: OR = 1.23, 95% CI: 0.86–1.76, P = .262; AA vs GG: OR = 1.05, 95% CI: 0.68–1.63, P = .820; AG vs AA: OR = 0.77, 95% CI: 0.53–1.13, P = .186; AG vs GG: OR = 0.89, 95% CI: 0.68–1.16, P = .376). In subgroup analysis by race, age, and disease type, we did not find any significant association. However, the presence of rs16754 GA/GG genotype was associated with improved overall survive (HR = 0.48, 95% CI: 0.26–0.91, P = .024) and relapse-free survival (HR = 0.82, 95% CI: 0.68–1.00, P = .048) compared with the rs16754 AA. In summary, the WT1 SNP rs16754 was not associated with AML risk, but it had a significant impact on clinical outcome in AML patients.

Abstract B05: Comprehensive functional modeling of pan-cancer risk SNP rs6983267 in human CRC cells via scarless CRISPR/Cas9 genome editing

Abstract With the continued emergence of genome-wide association study-identified risk loci for complex diseases as well as a sharp increase in the number of variants of uncertain significance (VUS) identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Our lab has previously published a novel variant modeling pipeline that combines CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) technology to create scarless isogenic cell models of cancer variants in ~1 month. In this study, we utilize our pipeline to model risk single-nucleotide polymorphism (SNP) rs6983267 in human colorectal cancer (CRC) cells and present the first functional characterization for this risk SNP at the most precise level possible with current technology, isogenic clones of the same cell lines that only differ by a single base. Rs6983267 is located within a known Myc enhancer and has been shown to exert risk-allele specific increase in enhancer activity. However, we do not observe risk-allele specific upregulation of Myc expression in our isogenic models. Instead, we find that presence of the risk allele confers significant effects within the cell locally, modulating activity of adjacent binding site for WNT transcription factor, TCF7L2, and a subset of genes associated with enhancer function. Through 3D interaction analysis, we identify difference in interactions in cis across the three genotypes including the loss of interaction with Myc in the heterozygous and homozygous reference lines, indicating genotype-specific changes of enhancer gene targets in CRC cells. Together, these variations lead to global effects, affecting transcriptional expression of genes involved in WNT signaling, cell-to-cell adhesion, and PI3K-Akt signaling pathways. These results suggest the loss of a single risk allele in CRC cells confers a transcriptional change associated with overall decreased cancer activity despite expression of the putative target gene of the enhancer, Myc, not being significantly affected. Interestingly, engineered loss of both risk alleles in CRC cells does not further the overall effect, indicating the activation of a compensatory mechanism, possibly due to redundancy of regulatory pathways affected. Activation of such compensatory mechanisms could demonstrate an important limitation to the use of established cancer cell lines in the functional modeling of risk-associated variants, which are the current standard models in the field. Our study provides an important contribution to the current efforts of functional characterization of novel VUSs and noncoding SNPs associated with cancer risk. It will become important to consider validation standards and functional thresholds for inclusion of lower penetrance susceptibility alleles in clinical decision-making as the field continues to advance towards the ultimate goal of precision medicine in cancer. Citation Format: Nicole B. Coggins, Henriette O'Geen, David J. Segal, Luis G. Carvajal-Carmona. Comprehensive functional modeling of pan-cancer risk SNP rs6983267 in human CRC cells via scarless CRISPR/Cas9 genome editing [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B05.

Associations of the microRNA gene polymorphisms with the risk of non-syndromic supernumerary teeth in a Chinese population

ObjectiveNon-syndromic supernumerary teeth (NSST) are a common type of dental anomaly. microRNAs (miRNAs) play an important role in craniofacial and tooth development. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) of miRNAs may be associated with the susceptibility of NSST. Materials and methodsFour miRNA SNPs (rs2910164, rs11614913, rs2043556, and rs2682818) were selected, and their associations with NSST susceptibility were evaluated in a case-control study (163 NSST patients and 326 healthy controls). Resultsrs2910164 was significantly associated with a risk of lower NSST (additive model: OR = 4.00, 95 % CI = 1.76–9.09, P = 0.001), and rs2682818 showed nominal association with a risk of upper NSST (additive model: OR = 1.40, 95 % CI = 1.02–1.91, P = 0.037) and NSST among male patients (additive model: OR = 1.62, 95 % CI = 1.08–2.43, P = 0.020). ConclusionGenetic variants of miR-146a/rs2910164 and miR-618/rs2682818 were likely associated with the risk of NSST in the Chinese population.

Predictive role of single nucleotide polymorphism (rs11614913) in the development of breast cancer in Pakistani population.

Aim:miRNAs play an important role in breast cancer (BC). Variations in miRNAs influence their maturation, expression and consequently regulation of their target genes. Materials & methods: In this study, single nucleotide polymorphism rs11614913 was genotyped in BC patients (n=300) and 230 controls by employing tetra primer amplification refractory mutation system PCR and Sanger sequencing (Macrogen Korea). Results: A significant difference was observed in the genotypes through co-dominant(χ2.#x00A0;=42.03; p<0.0001), additive(odds ratio [OR] =0.6441 [0.4887-0.8490, 95% confidence interval]; p<0.0019), dominant (OR=0.3996 [0.2809-0.5686], p<0.0001) and recessive (OR=0.2993 [0.1220-0.7347], p<0.009) statistical models showed decreased risk association of C allele with BC. Conclusion: Females having CT genotype are at higher risk of BC as compared with those having CC genotype.

A case of Philadelphia chromosome-positive acute myeloid leukaemia with missense mutation R132c (c.394 c&gt;t) and single nucleotide polymorphism rs11554137(G105G) in isocitrate dehydrogenase 1 gene

Acute myeloid leukaemia (AML) is a heterogeneous disease due to its variable clinical, morphological and genetic features. New chromosomal and molecular abnormalities are being studied to evaluate novel treatment options and prognostic implications. We report a patient with AML who was Philadelphia chromosome-positive along with IDH1R132 mutation and SNP rs11554137(IDH1105GGT). Due to limited reports regarding these aberrations in patients with AML, there is no consensus regarding their prognostic implications. To the best of our knowledge, the presence of Philadelphia chromosome, IDH1R132 and SNP rs11554137 in a single AML patient with good prognosis is a novel finding.

Single nucleotide polymorphisms Rs1045642 C&amp;gt;T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Single nucleotide polymorphisms Rs1045642 C&amp;gt;T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Single nucleotide polymorphisms Rs1045642 C&amp;gt;T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Breast cancer is one of the most devastating diseases in the world, the most diffused cancer in women. Despite the incredible progress made in the field, the mortality rate in the metastatic setting is still quite high. Among the different drugs used to treat this disease, the mTOR inhibitor everolimus is one of the most promising ones, that has been approved to be used together with exemestane in the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole, following the encouraging results coming from BOLERO-2 clinical trial showing a significant increase in progression-free-survival of patients compared to patients treated with exemestane and placebo. In this article we will discuss how the toxicity of this drug could be increased with Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 (ABCB1), a pump that expels this drug from the cells, leading to a more inactive ABCB1. With an inactivation of ABCB1 more everolimus would linger within the cancer cells, exerting more of its anti-tumor work. Future diagnosis of genetic alteration of Rs1045642 C>T in ABCB1 could be pivotal for determining if patients would benefit more from everolimus.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta‐analysis

BackgroundThe present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC).MethodsA systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression‐free survival (PFS) and disease‐free survival (DFS) were collected and analysed.ResultsTwenty‐four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30–2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19–3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results.ConclusionsThe MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well‐designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

Association between FokI, ApaI of vitamin D receptor gene polymorphism and idiopathic hypocitraturia

Objective To investigate the association between FokⅠ (rs2228570), ApaⅠ (rs7975232) of vitamin D receptor (VDR) gene polymorphism and idiopathic hypocitraturia (IH) in the Yunnan Yi population and its clinical significance in the large screening. Methods 501 cases of IH and 378 controls with normal urinary citrate were selected from the Yunnan Yi population, and the association between rs2228570 and rs7975232 VDR gene polymorphism with IH in the Yunnan Yi population was analyzed by SNaPshot detection. Results There were significant diferences in the practical fequency and expected fequency between the two single nucleotide polymorphism (SNP) sites in the hard—weinberg equilibrium (rs2228570: χ2=2.111, P>0.05; rs7975232: χ2=3.320, P>0.05). The mean urinary citrate content of 501 cases was (243.26±38.63) mg/24 h and that of 378 controls was (591.58±125.89) mg/24 h with the differences being statistically significant (t=34.263, P<0.05). There was significant difference in the genotype frequency difference of the VDR gene SNP rs2228570, rs7975232 (rs2228570: χ2=9.247, P<0.05; rs7975232: χ2=9.997, P<0.05) between cases and controls. The frequency of TT genotype (0.267) in the rs2228570 was higher than that in the control group (0.188), while the CT and CC genotype frequencies in the rs2228570 group were lower than those in the control group (χ2=9.899, P<0.05). The frequency of AA genotype (0.192) in the rs7975232 case group was higher than that in the control group (0.095), and the frequency of AA and CC genotypes in the case group was lower than that in the control group (χ2=15.696, P<0.05). The urinary citrate content of cases with rs2228570 genotype TT was significantly lower than that in those with genotype CC and genotype CT [(506.47±198.02) mg/24 h, t=6.276, P<0.05; (485.95±190.95) mg/24 h, t=4.709, P<0.05]. The urinary citrate content of cases with rs7975232 genotype AA was significantly lower than that in those with genotype CC and genotype CA [(507.67±197.42) mg/24 h, t=4.366, P<0.05; (485.55±180.15) mg/24 h, t=3.963, P<0.05]. Conclusion IH in the Yunnan Yi population has the association with rs2228570, rs7975232 VDR gene polymorphisms. Key words: Yunnan Yi population; Vitamin D receptor; Single nucleotide polymorphism; Idiopathic hypocitraturia

MiR-21 binding site SNP within ITGAM associated with psoriasis susceptibility in women.

BackgroundGreat progress has been made in the understanding of inflammatory processes in psoriasis. However, clarifying the role of genetic variability in processes regulating inflammation, including post-transcriptional regulation by microRNA (miRNA), remains a challenge.ObjectivesWe therefore investigated single nucleotide polymorphisms (SNPs) with a predicted change in the miRNA/mRNA interaction of genes involved in the psoriasis inflammatory processes.MethodsStudied SNPs rs2910164 C/G–miR-146a, rs4597342 T/C–ITGAM, rs1368439 G/T–IL12B, rs1468488 C/T–IL17RA were selected using a bioinformatics analysis of psoriasis inflammation-associated genes. These SNPs were then genotyped using a large cohort of women with psoriasis (n = 241) and healthy controls (n = 516).ResultsNo significant association with psoriasis was observed for rs2910164, rs1368439, and rs1468488 genotypes. However, the major allele T of rs4597342 –ITGAM was associated with approximately 28% higher risk for psoriasis in comparison to the patients with the C allele (OR = 1.28, 95% CI 1.01–1.61, p = 0.037). In case of genotypes, the effect of the T allele indicates the dominant model of disease penetrance as the CT and TT genotypes increase the chance of psoriasis up to 42% in comparison to CC homozygotes of rs4597342 (OR = 1.42, 95% CI = 1.05–1.94, p = 0.025).ConclusionSNP rs4597342 in 3'UTR of ITGAM influencing miR-21 binding may be considered a risk factor for psoriasis development. Upregulated miR-21 in psoriasis is likely to inhibit CD11b production in the case of the rs4597342 T allele which may lead to Mac-1 dysfunction, resulting in an aberrant function of innate immune cells and leading to the production of cytokines involved in psoriasis pathogenesis.

THE ROLE OF VITAMIN D, VITAMIN D RECEPTOR GENE FOKI POLYMORPHISM, AND CATHELICIDIN IN TUBERCULOSIS INFECTION IN CHILDREN

Objective: Recent studies have reported that vitamin D has an important role in tuberculosis. Polymorphism of single nucleotide polymorphism (SNP) rs2228570 or FokI will generate proteins with various amino acid lengths, and affect the molecular physiological roles of vitamin D. Cathelicidin acts as an antimicrobial directly against Mycobacterium tuberculosis (Mtb) and mediator autophagy by macrophages induced by vitamin D. This study aims to determine the role of vitamin D, vitamin D receptor gene SNP rs2228570 (FokI), and plasma levels of cathelicidin in children with tuberculosis infection.&#x0D; Methods: This cross-sectional was conducted on children aged £14 y who had close contacts with an adult who had sputum smear positive for acid-fast bacilli indicating pulmonary TB. The children were divided into two groups: those with and those without TB infection. Demographic data and blood samples were taken from children participating in this study to examine polymorphisms and cathelicidin plasma levels, and to determine the association between these levels in children with and without TB infection.&#x0D; Results: There were no differences in the proportion of genotype and allele of SNP rs2228570 vitamin D receptor gene (FokI), polymorphisms of VDR, and cathelicidin plasma levels between children with and without TB infection (p&gt;0.05). However, nutritional status and levels of cathelicidin by age category increased the risk of TB infection (p&lt;0.05).&#x0D; Conclusion: Cathelicidin level in children with TB infection lower than without. Vitamin D and FokI polymorphism did not play role in TB infection.

The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A.

The complex interplay among genetic, epigenetic, and environmental variables is the basis for the multifactorial origin of age-related macular degeneration (AMD). Previous results highlighted that single nucleotide polymorphisms (SNPs) of CFH, ARMS2, IL-8, TIMP3, SLC16A8, RAD51B, VEGFA, and COL8A1 were significantly associated with the risk of AMD in the Italian population. Given these data, this study aimed to investigate the impact of SNPs in genes coding for MIR146A, MIR31, MIR23A, MIR27A, MIR20A, and MIR150 on their susceptibility to AMD. Nine-hundred and seventy-six patients with exudative AMD and 1000 controls were subjected to an epigenotyping analysis through real-time PCR and direct sequencing. Biostatistical and bioinformatic analysis was performed to evaluate the association with susceptibility to AMD. These analyses reported that the SNPs rs11671784 (MIR27A, G/A) and rs2910164 (MIR146A, C/G) were significantly associated with AMD risk. Interestingly, the bioinformatic analysis showed that MIR27A and MIR146A take part in the angiogenic and inflammatory pathways underlying AMD etiopathogenesis. Thus, polymorphisms within the pre-miRNA sequences are likely to affect their functional activity, especially the interaction with specific targets. Therefore, our study represents a step forward in the comprehension of the mechanisms leading to AMD onset and progression, which certainly include the involvement of epigenetic modifications.

MicroRNA-196a2 single nucleotide polymorphism rs11614913 in Egyptian patients with chronic lymphocytic leukemia

Background: MicroRNAs are recently identified class of small single stranded RNA molecules of 21-23 nucleotides that regulate gene expression at the posttranscriptional level. Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis resulting in accumulation of mature resting B cells within the peripheral blood, bone marrow and lymphoid organs. One of the relevant microRNAs to CLL is microRNA-196a2, as its potential targets of action include genes involved in apoptosis regulation. The single nucleotide polymorphism (SNP) in microRNA-196a2 rs11614913 C/T has been implicated as possible biomarker associated with multiple kinds of cancers. While multiple recent studies showed that genetic polymorphisms play an influential role in CLL susceptibility, the role of microRNA-196a2 SNP rs11614913in CLL remains elusive. Patients and methods: The present study was conducted on 40 newly diagnosed Egyptian CLL patients and 40 control subjects. Genotyping of microRNA-196a2 SNP rs11614913 was performed by real-time PCR. Results: The CC genotype was found in 55% of CLL patients versus 12.5% of the controls.On the other handthe TT and TC genotypes were significantly predominant in the control group compared to CLL patients with frequencies of 25% and 62.5% versus 10% and 35% respectively (p&lt;0.001). The C allele carriers were found to have 3.38 fold increased risk for development of CLL (OR=3.38, CI=1.75–6.56) while the T allele seems to be protective against CLL (OR=0.29, CI=0.15–0.57). Conclusion: We could conclude that the CC genotype and the C allele of miR-1962a SNP rs3217927are implicated in the risk of CLL development in Egyptian patients while the T allele has a protective effect. However, additional well-designed large studies are required for the validation of these associations

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population.

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.

MiRNA-146a polymorphism increases the odds of malaria in pregnancy

BackgroundPlasmodium falciparum infection during pregnancy is a major cause of poor maternal health, adverse foetal outcome and infant mortality in sub-Saharan Africa. Genetic disposition is involved in susceptibility to malaria in pregnancy and its manifestation. MicroRNAs (miRNAs) influence gene regulation including that of innate immune responses. A miRNA-146a rs2910164 G > C single nucleotide polymorphism (SNP) has been associated with increased risks of several diseases, but no data as to malaria are available.MethodsThe association between miRNA-146a rs2910164 and P. falciparum infection among 509 Ghanaian women attending antenatal care (ANC) and 296 delivering Ghanaian primiparae was investigated. Malaria parasites were diagnosed by microscopy and PCR. Leukocyte-associated hemozoin in placental samples was recorded as well. Proportions were compared between groups by Fisher’s exact test, and logistic regression models were used to adjust for possible confounders.ResultsBy PCR, P. falciparum infection was detected in 63% and 67% of ANC attendees and delivering primiparae, respectively. In both groups, two in three women were either heterozygous or homozygous for miRNA-146a rs2910164. Among ANC attendees, homozygosity conferred increased odds of infection (adjusted odds ratio (aOR), 2.3; 95% CI, 1.3–4.0), which was pronounced among primigravidae (aOR, 5.8; 95% CI, 1.6–26) but only marginal in multigravidae. Likewise, homozygosity for miRNA-146a rs2910164 in primiparae increased the odds of past or present placental P. falciparum infection almost six-fold (aOR, 5.9; 95% CI, 2.1–18).ConclusionsThese results indicate that SNP rs2910164 G > C is associated with increased odds for P. falciparum infection in first-time pregnant women who are considered to lack sufficient acquired immune responses against pregnancy-specific strains of P. falciparum. These findings suggest that miRNA-146a is involved in protective malarial immunity, and specifically in the innate component.

Influence of ABCB1 C3435T and C1236T gene polymorphisms on tumour response to docetaxel-based neo-adjuvant chemotherapy in locally advanced breast cancer patients of South India.

Variable response to docetaxel-based neo-adjuvant chemotherapy (NACT) in breast cancer patients had been reported. Genetic polymorphisms in the ABCB1 gene coding for the efflux transporter MDR1 (P-glycoprotein, P-gp) could result in altered tumour response. Hence, this study was proposed to assess the effect of single nucleotide polymorphisms (SNPs) of ABCB1 gene on tumour response in locally advanced breast cancer patients (LABC) of South India who have a distinct genetic makeup. Out of 162 LABC patients recruited, 129 patients were included for the final analysis. DNA was extracted by "phenol-chloroform extraction method" from the WBCs, and genotyping for SNPs rs1045642 (C3435T) and rs1128503 (C1236T) in ABCB1 gene was performed with real-time PCR system using validated TaqMan® SNP genotyping assay method. Tumour response was assessed by RECIST criteria based on the MRIs taken before and after completion of four cycles of docetaxel therapy. A total of 102 (79.1%) patients were found to be responders and 27 (20.9%) patients were found to be non-responders to docetaxel therapy. Patients with "CT/TT" genotypes (response rate: 83.3%) of ABCB1 (C1236T) gene showed better tumour response than those with "CC" genotype (response rate: 16.6%) [OR=2.94 (CI: 1.15-7.52); P=0.03]. However, on performing binary logistic regression, neither the studied SNPs nor the non-genetic factors like age, BMI, postmenopausal status, laterality of the tumour, ER status, PR status and Her-2/neu status were found to be associated with tumour response to docetaxel (P>0.05). The tumour response to docetaxel was significantly influenced by the SNP C1236T of ABCB1 gene coding for the P-gp. However, when adjusted for other non-genetic factors, neither of the ABCB1 variants were found to be associated with tumour response to docetaxel-based NACT in LABC patients of South India.