Significant Allelic Differences Research Articles

Association of VEGFR1, VEGFR2 and VEGFR3 polymorphisms with esophageal cancer risk: a case–control study

BackgroundEsophageal cancer is the eleventh most common cancer and is the seventh leading cause of mortality worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway are a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFR polymorphisms with esophageal cancer risk in patients from Punjab, North-west India.MethodsThis case–control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1-710C/T, VEGFR2-604 T/C (rs2071559), VEGFR2 1192 G/A (rs2305948), VEGFR2 1719A/T (rs1870377) and VEGFR3 (rs72816988) polymorphisms were genotyped by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Restriction digestion products were analyzed on 2.4% agarose gel and genotype was assigned to each sample on the basis of fragments obtained after digestion. Randomly 10% samples were repeated by Sanger sequencing to revalidate the results.ResultsThere was a significant association of CT genotype (OR = 0.28; 95%CI, 0.10–0.76; p = 0.01) and T allele (OR = 0.28; 95%CI, 0.10–0.77; p = 0.01) of VEGFR1-710C/T polymorphism with decreased risk of esophageal cancer. TC genotype of VEGFR2-604 T/C (OR = 0.66; 95%CI, 0.44–0.97; p = 0.03) and GA genotype of VEGFR2 1192G/A (OR = 0.54; 95%CI, 0.31–0.95; p = 0.03) polymorphisms were significantly associated with decreased risk of esophageal cancer. There was no significant difference in allele and genotype frequency of VEGFR2 1719A/T and VEGFR3 (rs72816988) polymorphisms between esophageal cancer patients and controls (p > 0.05). Haplotype analysis revealed that haplotype C-604A1719A1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01).ConclusionVEGFR1-710C/T, VEGFR2-604 T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-west India.Graphical abstract

Differences in ACTN3 Genotype in Professional Ssireum Players Between Weight Classes and Elite/Non-Elite Status

PURPOSE This study aimed to identify ACTN3 gene polymorphisms amongprofessional ssireum players by weight class and between elite and non-elite players,and to select genotype that matches the characteristics of the sport. METHODS The subjects of this study were 148 male athletes currently working as professionalssireum players. Chi-square test cross-tabulation analysis was conducted to examinethe differences in ACTN3 genotypes between weight classes and between elite andnon-elite players. RESULTS There were no significant differences in allele or genotypebetween ssireum players, but there were significant differences in R-allele and XXgenotype. CONCLUSIONS Players with the R-allele type of the ACTN3 gene weremore often classified as elite. Using this marker as a basis for organizing a playerselection and training programs would be more effective in training those that matchthe characteristics of elite players of the game.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Detection of vacA gene alleles frequency in Helicobacter pylori strains from patients with gastric diseases in Zliten city Libya

Helicobacter pylori (H. pylori) has worldwide distribution, leading to various gastric diseases, including chronic gastritis, peptic ulcer and gastric cancer. A vacA gene, which encodes a vacuolating cytotoxin is one of the most known virulence gene of the bacterium. The aim of this study was to evaluate the most common vacA alleles (s1 and s2) in H. pylori strains isolated from Libyan patients and its relationship with ages and gastritis lesions. Gastric biopsies were obtained from patients for DNA extraction. vacA genotypes were analyzed by PCR and agarose electrophoresis. s1 and s2 genotypes were also confirmed by DNA sequencing. The allele s2 occurred in 81% of the all examined group, which represent the most frequently observed of the signal encoding region. Whereas s1 genotype had the lowest frequency 19%. Statistically significant differences in s1 and s2 alleles in relation to a ages were not detected. This study showed that there was a relationship between the presence of vacA gene and progression of gastritis. the predominant vacA gene alleles in Zliten city is s2 allele.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis

BackgroundLong non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility.MethodsA total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls.ResultsNo significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls.ConclusionsOur study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option

BackgroundPreeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.ObjectiveThis study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.MethodsIn this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.ResultsOur statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.ConclusionsNo risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

Correlation analysis of IL-37 gene polymorphisms and susceptibility to chronic HBV infection among Han people in Central China.

Hepatitis B virus (HBV) is responsible for various liver diseases, such as chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which pose a significant threat to human health. An ineffective immune response to HBV can result in viral chronicity. Interleukin-37 (IL-37), an immunomodulator, is capable of inhibiting both innate and adaptive immune responses. It is believed that single nucleotide polymorphisms (SNPs) within the IL-37 gene could contribute to the regulation of HBV clearance. Our aim to conduct this study was to investigate whether SNPs in the IL-37 gene were associated with the risk of chronic HBV infection in adults. A total of 342 participants, consisting of 171 cases and 171 controls, were recruited for this study. Sanger sequencing was employed for genotyping six SNPs (rs3811042 G/A, rs3811043 G/C, rs2466449 A/G, rs3811045 C/T, rs3811046 T/G and rs3811047G/A). There was no significant difference in allele and genotype distribution between the two groups, and the constructed haplotypes were not found to be associated with the risk of chronic HBV infection. Our results revealed that there was no relationship between these six SNPs (rs3811042G/A, rs3811043G/C, rs2466449A/G, rs3811045C/T, rs3811046T/G and rs3811047G/A) in the IL-37 gene and susceptibility to chronic HBV infection among Han people in Central China.

Relationship between Prolactin rs1341239 Gene Polymorphism and Prolactin Serum Level in Iranian Patients with Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus (SLE) as an inflammatory autoimmune disease, originates from the production of autoantibodies against several cellular components, especially nuclear components such as DNA. Prolactin consists of 199 amino acids and due to the structural similarity with cytokines, this polypeptide has the ability to modulate the immune system, which is characterized by the observation of hyperprolactinemia in autoimmune disorders. The rs1341239 polymorphism of the prolactin gene is associated with several autoimmune diseases. The purpose of this study is to investigate the relationship between this polymorphism and prolactin serum level in SLE patients in a population from Iran.
 Methods: Genotype analysis of prolactin rs1341239 gene polymorphism was performed using blood samples of 90 SLE patients as patients’ group and 90 control samples as the control group through RFLP-PCR method. Also, serum prolactin concentration was measured using ELISA method.
 Results: Our results showed a significantly higher serum level of prolactin in patients group than in the control group. There was no significant difference in alleles and genotypes frequencies of rs1341239 polymorphism in patients group compared to the control group. However, a significant correlation was found between the frequency of GG genotype and the reduction of platelets in the blood of patients group.
 Conclusion: Our results did not show a significant difference in the frequency of prolactin rs1341239 gene polymorphism in patients and control groups, while we observed the relationship between this polymorphism and platelet count in patients group.

Pityriasis Versicolor: host susceptibility in relation to IL-10 and IFN γ cytokine gene polymorphism

Pityriasis Versicolor is a skin condition caused by the commensal yeast Malassezia. Little is known about the pathogenesis of why a commensal only causes symptoms in a subset of infected individuals. Understanding the susceptibility of the host to these commensal-associated diseases may be facilitated by knowledge of genetic polymorphism. The purpose was to investigate the relationship between Single Nucleotide Polymorphism in the IL10 and IFN genes of the host and susceptibility to Malassezia infection. There were 38 cases of Pityriasis Versicolor (PV) and 38 healthy controls in the sample. Blood samples were extracted for genomic DNA from all study participants. Amplification refractory mutations system- polymerase chain reaction (ARMS-PCR) with sequence-specific primers was used to genotype cytokines. In all patients and healthy controls, three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN- +874A/T) in two cytokine loci were analyzed. In the PV group, we observed significant differences in allele or genotype distribution for the IL10-819/592C/T and IFN- +874A/T gene polymorphisms. In the present investigation, cytokine gene polymorphism revealed that the host was susceptible to Malassezia infection.

Genome wide association studies and candidate gene mining for understanding the genetic basis of straw silica content in a set of Oryza nivara (Sharma et Shastry) accessions.

Rice is a high-silica (SiO2·nH2O) accumulator. Silicon (Si) is designated as a beneficial element associated with multiple positive effects on crops. However, the presence of high silica content is detrimental to rice straw management, hampering its use as animal feed and as raw material in multiple industries. Rice straw management is a serious concern in north-western India, and it is eventually burned in situ by farmers, contributing to air pollution. A practical solution could lie in reducing the silica content in rice while also attaining sound plant growth. A set of 258 Oryza nivara accessions along with 25 cultivated varieties of Oryza sativa was used to assess the variation in straw silica content using the molybdenum blue colorimetry method. A large continuous variation was observed for straw silica content in O. nivara accessions, ranging from 5.08% to 16%, while it varied from 6.18% to 15.81% in the cultivated varieties. The O. nivara accessions containing 43%-54% lower straw silica content than the currently prominent cultivated varieties in the region were identified. A set of 22,528 high-quality single nucleotide polymorphisms (SNPs) among 258 O. nivara accessions was used for estimating population structure and genome-wide association studies (GWAS). A weak population structure with 59% admixtures was identified among O. nivara accessions. Further, multi-locus GWAS revealed the presence of 14 marker-trait associations (MTAs) for straw silica content, with six of them co-localizing with previously reported quantitative trait loci (QTL). Twelve out of 14 MTAs showed statistically significant allelic differences. Thorough candidate gene analyses revealed the presence of promising candidate genes, including those encoding the ATP-binding cassette (ABC) transporter, Casparian thickening, multi-drug and toxin extrusion (MATE) protein, F-box, and MYB-transcription factors. Besides, ortho-QTLs among rice and maize genomes were identified, which could open ways for further genetic analysis of this trait. The findings of the study could aid in further understanding and characterizing genes for Si transport and regulation in the plant body. The donors carrying the alleles for lower straw silica content can be used in further marker-assisted breeding programs to develop rice varieties with lower silica content and higher yield potential.

MMP2 rs243866 and rs2285053 Polymorphisms and Alzheimer's Disease Risk in Slovak Caucasian Population.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by progressive loss of memory. In the AD brain, matrix metalloproteinases (MMPs) are involved in the disruption of the blood-brain barrier resulting in a neuroinflammatory response. The objective of our investigation was to assess the association of MMP2 rs243866 and rs2285053 polymorphisms with susceptibility to AD, to assess the interaction of MMP2 variants with APOE ε4 risk allele, and to evaluate their influence on the age at disease onset and MoCA score. A total of 215 late-onset AD patients and 373 control subjects from Slovakia were genotyped for MMP2 rs243866 and rs2285053 polymorphisms. The MMP2 association with AD risk and clinical parameters was evaluated by logistic and linear regression analyses. No statistically significant differences in either MMP2 rs243866 and rs2285053 allele or genotype frequencies between AD patients and the control group have been observed (p > 0.05). However, the correlation with clinical findings revealed a higher age at disease onset in MMP2 rs243866 GG carriers in the dominant model as compared to other MMP2 genotype carriers (p = 0.024). Our results suggest that MMP2 rs243866 promoter polymorphism may have an impact on the age at AD onset in the patients.

Association between ACTN3 R577x and the physical performance of Chinese 13 to 15-year-old elite and sub-elite football players at different positions.

The purpose of this study was to investigate the prevalence of ACTN3 polymorphisms in Chinese elite and sub-elite football players aged 13-15years at different positions. Specifically we explored whether ACTN3 genotypes were linked with athletic performance of elite and sub-elite players at different positions. The RR genotype frequency of elite defenders (p = 0.018) and midfielders (p = 0.008) was significantly higher than that of sub-elite XX genotype in elite players. Furthermore, the R allele frequency of elite defenders (p = 0.003) and midfielders (p = 0.008) was significantly higher than that of sub-elite players. In all subjects, RR players performed faster and exhibited more explosive power than RX or XX players. RR, RX and XX elite players' 20m/30m sprint, 5 × 25-m repeated sprint ability (5 × 25m RSA), and standing long jump were stronger than sub-elite players, but there was no significant different in aerobic endurance between elite and sub-elite players at different positions. In conclusion, there were significant differences in ACTN3 genotypes and alleles between elite and sub-elite players at different positions, and the RR genotype was significantly associated with power-related athletic performance in Chinese youth football players.

Cholesterol 7α-Hydroxylase Gene-204A/C Polymorphism in Normal and Gestational Diabetic Pregnancies

To investigate the cholesterol 7α-hydroxylase gene ( CYP7A1)-204A/C single nucleotide polymorphism and its relationship with the blood lipid levels of pregnant women with gestational diabetes mellitus (GDM) and normal pregnant women. The genotype and allele frequencies of CYP7A1-204A/C gene polymorphism of 1037 normal pregnant women, the normal controls, and 627 pregnant women with GDM were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and blood glucose (Glu) were measured by enzymatic assay. Chemiluminescence determination of plasma insulin (Ins) was conducted. Apolipoproteins A1 (apoA1) and B (apoB) were measured by the turbidimetric immunoassay. Allele frequencies of A and C at the CYP7A1-204A/C polymorphic locus were 0.586 and 0.414, respectively, in the GDM group and 0.557 and 0.443, respectively in the control group. The distribution of genotype frequencies in both groups showed conformity with the Hardy-Weinberg principle. There was no significant difference in allele and genotype frequencies between the GDM group and the control group. In the control group, carriers of the genotype AA were associated with significantly higher concentrations of apoA1 and lower levels of Ins and homeostatic model assessment of insulin resistance (HOMA-IR) compared with those with genotype CC (all P<0.05). In the non-obese subgroup of the control subjects, carriers of the genotype CC were associated with significantly higher plasma TG or apoA1 levels compared with those with genotype AA ( P<0.05). In the GDM group, carriers with genotype AA of CYP7A1-204A/C polymorphism had elevated levels of gestational weight gain (GWG) compared with those with genotype CC ( P<0.05). These results suggest that 204A/C polymorphism in the CYP7A1 gene is not associated with GDM, but may be closely associated with gestational weight gain in pregnant women with GDM. Variants in this locus are strongly associated with plasma apoA1, Ins, and HOMA-IR levels in the controls and elevated plasma TG levels in non-obese controls.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in patients with laryngeal cancer.

The aim of this study was to compare the distribution of the angiotensin-converting enzyme (ACE) I/D polymorphism between patients with laryngeal cancer (LC) and a control group and to examine the distribution of this polymorphism with clinical parameters related to LC. We enrolled 44 LC patients and 61 healthy controls. The ACE I/D polymorphism was genotyped with the PCR-RFLP method. The distribution of ACE genotypes (II, ID, and DD) and alleles (I or D) was evaluated with Pearson's chi-square test, and logistic regression analysis was performed for statistically significant parameters. There was no significant difference in ACE genotypes and alleles between LC patients and controls (p = 0.079 and p = 0.068, respectively). Among clinical parameters related to LC (extension of tumour, node metastasis, tumour stage and tumour location), only the presence of node metastasis was found to be significant in terms of ACE DD genotype (p = 0.137, p = 0.031, p = 0.147, p = 0.321 respectively). In the logistic regression analysis, the ACE DD genotype was increased 8.3 fold in nodal metastases. The findings of the study suggest that ACE genotypes and alleles do not affect the prevalence of LC, but the DD genotype of ACE polymorphism may increase the risk of lymph node metastasis in LC patients.

Virulence determinants and genotypes of &lt;i&gt;Helicobacter pylori&lt;/i&gt; clinical isolates

Background. H. pylori is the principal causative agent of gastroduodenal disorders in humans. The development and severity of lesions in infected individuals depend on the virulence of H. pylori strains.&#x0D; Aims: Detection of virulence determinants and comparative analysis of H. pylori genotypes in patients with chronic gastritis (CG) and duodenal ulcer (DU).&#x0D; Materials and methods. The 53 H. pylori strains were isolated in St. Petersburg from patients with CG (n = 34) and DU (n = 19). The genetic determinants of virulence cagA, iceA, vacA and H. pylori genotypes in patients with CG and UC were determined using the standard PCR method.&#x0D; Results. The cagA gene was found in 64.1% of H. pylori strains. The proportions of cagA+ isolates from patients with CG and DU was 55.8% (15/34) and 78.9% (15/19), respectively (p 0.05). The iceA1 allele of H. pylori was detected in 47.4% of patients with DU, the iceA2 in 47.1% of patients with CG (p 0.05). The vacAs1 allele was significantly dominant in patients with DU 94.7% versus 70.6% in CG (p 0.05). No significant difference in vacA m1 and m2 alleles was found in H. pylori from different groups of patients (p 0.05). All cagA+ strains were carriers of the vacA s1 allele. The vast majority of strains (10 out of 11) of the cagA/vacAs2 genotype were isolated from patients with CG.&#x0D; Conclusion. The significant association between vacAs1, vacAs2 allelic variants, as well as vacA s1/m2, vacA s2/m2 genotypes of the pathogen and severity of clinical manifestations of H. pylori infection has been established in our study. The vacAs1 and vacA s1/m2 genotypes of the pathogen are associated with duodenal ulcer.

The relationship of E-selectin singlenucleotide polymorphisms with breast cancer in Iraqi Arab women.

Breast cancer (BC) is a significant threat to female health, with both modifiable andnon-modifiable risk factors. It is essential to monitor patients regularly and to raise population awareness. Increasing research also suggests that E-selectin (SELE) may increase tumor angiogenesis and the development of cancer. This study investigated SELE single-nucleotide polymorphisms (SNPs) in the following positions: rs5367T/C, rs5368C/T, rs5362T/G,and rs5362T/C. Using polymerase chain reaction, significant differences in allele and genotype frequencies were found between BC patients and controls. Position rs5368 was associated with an increased risk of BC for the CT and TT genotypes, with odds ratios (ORs) of16.3 and 6.90 (Fisher probability = 0.0001, p = 0.005). Women with the T allele had a 19.3-fold higher incidence of BC, while allele C may be a protective allele against BC (OR, 0.05).Heterozygous genotypes at rs5367, rs5362, and rs5362 were significantly more common inBC patients, with ORs of 5.70, 4.50, and 3.80, respectively. These SNPs may be associatedwith the risk of BC, because the frequency of mutant alleles was significantly higher in patients (OR: 4.26, 3.83, and 4.30, respectively) than in controls (OR: 0.23, 0.30, and 0.20, respectively). These SNPs may be considered a common genotype in the Iraqi population,with the wild-type allele having a protective fraction and the mutant allele having an environmental fraction. The results also revealed a 2-fold increase in gene expression in BCpatients compared to controls, with a significant effect (p = 0.017). This study's findingsconfirm the importance of SELE polymorphisms in cancer risk prediction.

Comparing the VDR Gene BsmI and CDX2 Polymorphisms in Healthy Turks and Healthy Somalians Living in Turkiye

Objectives: This study aimed to evaluate genotypic and allelic differences by comparing the Vitamin D (Vit-D) receptor (VDR) gene BsmI (rs1544410) and CDX2 (rs11568820) polymorphisms in healthy Turks and healthy Somalians living in Turkiye. Materials and Methods: The study involved 100 healthy Turkish individuals and 60 healthy Somali individuals residing in Turkiye for at least 5 years. The genotyping study was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) and allele-specific PCR methods. Statistical analysis was performed to identify the possible differences between groups using the Chi-square and Student’s t tests for pair-wise comparisons. Results: According to the data obtained in the study with regard to the BsmI (rs1544410 A/G) and CDX2 (rs11568820 A/G) genotypes, no statistically significant difference was determined to be present regarding the frequency of carrying the mutant GG genotype in the two groups (p = 0.95 and p = 0.221, respectively). Conclusion: The study has found no significant genotypic or allelic difference to be present in terms of the BsmI (rs1544410) and CDX2 (rs11568820) gene variants between healthy Turkish individuals and Somali individuals who have spent most of their lives exposed to less sunlight while living in Turkiye for the past five years.

Abstract 15063: Liver Gene Regulatory Mechanisms of Variants at Lipid and Cardio Metabolic Trait Loci

Genome-wide association studies (GWAS) have identified hundreds of risk loci for cardiometabolic and lipid-related traits. GWAS loci are enriched in tissue-specific transcriptional regulatory elements that affect target gene expression driving physiological changes. Most GWAS variants are located in non-coding regions, which makes identifying functional variants and target genes challenging. Previously, we identified GWAS signals colocalized with molecular quantitative trait loci for liver gene expression (eQTL) and liver accessible chromatin (caQTL) to predict regulatory variants for lipid and cardiometabolic traits. These caQTLs are rs13395911, rs11644920, rs34003091 and rs9556404 associated with liver enzymes, LDL-cholesterol, and triglycerides. To evaluate the predicted mechanisms, we tested these variants with surrounding regulatory elements for allelic effects on transcriptional reporter activity and for effects on target gene expression in HepG2 cell line. Along with the two previously reported intronic caQTL variants, rs13395911 and rs11644920 , we observed significant (P&lt;0.05) allelic differences in transcriptional activity for rs9556404 and rs34003091, located at the promoters of GPR180 and ZNF329 , respectively. Based on eQTL and HiC data, the predicted genes for intronic enhancers rs13395911 and rs11644920 are EFHD1 and LITAF , respectively. To confirm the target genes for these two variants, we deployed inducible CRISPRi system by stably expressing dCas9 fused to a KRAB-repressor domain in HepG2 and targeting guide RNAs (gRNAs) to the DNA elements that span caQTL variants. For each element, we introduced ≥6 gRNAs into cells via lentiviruses and measured gene expression using qPCR. Compared to pools of non-targeted control gRNAs, preliminary analyses using pools of enhancer-targeting gRNAs surrounding rs13395911 and rs11644920 led to 30.3% lower EFHD1 and 38.6% lower LITAF expression at 7 days post-transduction, respectively. Thus, we identified and validated mechanisms by which DNA variants alter transcriptional activity and identified the target genes for lipid-related GWAS loci. These results suggest that this framework can be scaled up to map thousands of enhancers to genes in their native genomic state.

Importance of selected ABCB1 SNPs for the level of severity of depressive symptoms and effectiveness of recurrent depressive disorder therapy

The expression level of mRNA and also the function of P-gp are strictly connected with the polymorphic nature of the ABCB1 gene. In this study, we evaluated the association between promoter SNP, i.e. T-129C, three other SNPs investigated earlier and ABCB1 expression in the depression group. To assess the additive significance of these SNPs on clinicopathological features a mathematical model was also built.102 patients suffering from recurrent depressive disorder (rDD) and 94 healthy individuals from a local blood bank were enrolled in this study. ABCB1 gene polymorphism was identified by the RFLP method. The relative level of ABCB1 expression was measured by real-time PCR.For SNP T-129C no statistically significant differences in allele and genotype frequencies between depression and control groups were found (p = 0.3176). There was no statistically significant association between the expression value and 4 studied SNPs in ABCB1 (T-129C, C1236T, G2677T/A and C3435T) or the investigated clinicopathological features. Furthermore, a correlation between the initial HDRS score (lower than 23) and presence of at least 1236 T allele was observed, in particular in combination with 3435 T or 2677 T/A. Mutated allele of each SNP was also significantly associated with declined response to antidepressant therapy, both individually and in combination with others.Results of this study suggest that T-129C does not play an important role in the rDD development. The influence of the studied SNPs on ABCB1 gene expression is still unknown. However, the additive impact of 3 most frequently studied SNPs of ABCB1 on the course of depression and effectiveness of its treatment was confirmed.