Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis.

There is little data regarding the impact of renin-angiotensin system (RAS) gene polymorphisms on tuberculosis. The current study designed to survey the possible association between RAS polymorphisms and the risk of pulmonary tuberculosis (PTB) in a sample of the southeast Iranian population. This case-control study was done on 170 PTB patients and 170 healthy subjects. The AGT rs699 C>T, ACE rs4341 C>G and AT1R rs5186 C>A variants were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and ACE rs4646994 (287bp I/D) variant by PCR method. Regarding AT1R rs5186 A>C polymorphism, the findings revealed that AC genotype and C allele significantly decreased the risk of PTB (OR=0.39, 95% CI=0.22-0.67, p=0.001, and OR=0.53, 95% CI=0.25-0.72, p=0.002, C vs. A, respectively). The TC genotype and C allele of AGT rs699 T>C significantly associated with decreased the risk of PTB (OR=0.45, 95% CI=0.28-0.74, p=0.002, TC vs. TT and OR=0.51, 95% CI=0.32-0.80, p=0.005, C vs. T, respectively). The ID genotype of ACE 287bp I/D significantly increased the risk of PTB (OR=1.88, 95% CI=1.12-3.17, p=0.017). Our finding did not support an association between ACE rs4341 C>G variant and the risk of PTB. In summary, the findings revealed an association between AT1R rs5186 A>C, AGT rs699 T>C and ACE 287bp I/D polymorphisms and the risk of PTB in a sample of the southeast Iranian population. Further investigation with higher sample sizes and diverse ethnicities are required to confirm our findings.

Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Association of Genetic Polymorphisms of GREM1 Gene with Susceptibility to Non-Syndromic Cleft Lip with or without Cleft Palate in an Iranian Population.

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is common congenital birth anomaly with multifactorial etiology. The GREM1 gene has been proposed to play a role in oral clefts development.Objective: The aim of the present study was to evaluate the correlation between GREM1 polymorphisms and the risk of NSCL/P in an Iranian population.Methods: Genotyping of rs7162202, rs12915554, rs3743105, rs1129456, and rs10318 polymorphisms of GREM1 gene in 150 NSCL/P and 152 healthy subjects was determined by the PCR-RFLP or T-ARMS-PCR.Results: The findings showed that the rs12915554 variant significantly increased the risk of NSCL/P in heterozygous (OR = 4.20, 95%CI = 2.46-7.11, p < 0.0001, AC vs AA), and allele (OR = 3.17, 95%CI = 2.00-5.08, p < 0.0001, C vs A) genetic models. The rs3743105 polymorphism was correlated with reduced risk of NSCL/P in heterozygous (OR = 0.49, 95%CI = 0.29-0.83, p = 0.008, AG vs GG) and dominant (OR = 0.54, 95%CI = 0.33-0.89, p = 0.018, GA + AA vs GG) genetic models. The rs1129456 variant was positively associated with the risk of NSCL/P in heterozygous (OR = 2.91, 95%CI = 1.12-7.38, p = 0.028, AT vs AA) and allele (OR = 2.80, 95%CI = 2.80-6.95, p = 0.031, T vs C). The rs10318 polymorphism significantly reduced NSCL/P risk in homozygous (OR = 0.20, 95%CI = 0.06-0.67, p = 0.013, TT vs CC), dominant (OR = 0.57, 95%CI = 0.36-0.91, p = 0.019, CT + CC vs CC), recessive (OR = 0.24, 95%CI = 0.07-0.76, p = 0.031, TT vs CT + CC), and allele (OR = 0.57, 95%CI = 0.38-0.84, p = 0.005, T vs C). No correlation was observed between rs7162202 polymorphism and NSCL/P.Conclusion: The findings support that GREM1 polymorphisms are involved in NSCL/P susceptibility in an Iranian population.

Association Study of MBL2 Gene Polymorphisms and Risk of Tuberculosis in Southeast of Iran.

Mannose-binding lectin (MBL) is an acute phase protein which recognizes the pathogens through its carbohydrate recognition domain. It is an important part of human innate immunity. The aim of the current study was to evaluate the impact of MBL2 polymorphism on pulmonary tuberculosis in a number of patients from the southeast of Iran. In this case-control study, 2 MBL gene polymorphisms (rs1800450, rs7095891) were genotyped using PCR-RFLP method and polymerase chain reaction for detection of 34bp ins/del of MBL2 gene (rs777980157) polymorphism. The study included 170 patients with PTB (pulmonary tuberculosis) and 175 control subjects. The findings indicated that the GA (GA vs. GG: OR=0.172, 95% CI=0.107-0.275, P<0.001) (OR - odds ratio; CI - confidence interval) genotype as well as GA+AA (GA+AA vs. GG: OR=0.191, 95% CI=0.120-0.302, P<0.001) genotype of rs1800450 reduced the risk of PTB compared to GG genotype. The rs7095891 variant significantly decreased the risk of PTB in codominant (GA vs. GG: OR=0.118, 95% CI=0.054-0.258, P<0.001; and AA vs. GG: OR=0.029, 95% CI=0.01-0.082, P<0.001), dominant (GA+AA vs. GG: OR=0.095, 95% CI=0.044-0.207, P<0.001) and recessive (AA vs. GA+GG: OR=0.172, CI=0.081-0.365, P<0.001) inheritance models. No significant relationship was identified between the rs777980157 variant and PTB risk/protection. In conclusion, we found that the MBL2 rs1800450 and rs7095891 polymorphisms provide relative protection against PTB. Additional studies on larger populations with different ethnicities are required to verify our findings.

Association between miR-34b/c rs4938723 polymorphism and risk of cancer: An updated meta-analysis of 27 case-control studies.

Several studies investigated the association between miR-34b/c rs4938723 polymorphism and the risk of several human cancers, but the findings remain inconclusive. To evaluate the impact of miR-34b/c rs4938723 on cancer risk, we performed a meta-analysis on all available studies including 12 361 cancer cases and 14 270 controls. Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Google scholar databases. Pooled odds ratios with 95% confidence intervals were calculated in codominant, dominant, recessive, overdominant, and allele models to quantitatively estimate the association. The overall findings showed no significant association between miR-34b/c rs4938723 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model. However, in stratified analysis by cancer types, the rs4938723 polymorphism significantly increased the risk of gastrointestinal cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was associated with decreased risk of esophageal squamous cell carcinoma, colorectal cancer, and acute lymphoblastic leukemia. The findings did not support an association between rs4938723 variant and digestive tract as well as gastric cancer. In summary, the findings of this meta-analysis indicated that the miR-34b/c rs4938723 polymorphism might be associated with some cancer development. Larger and well-designed studies are necessary to estimate this association in detail.

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population, a preliminary report.

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case-control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14-5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06-5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02-2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15-0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22-0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19-12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09-14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.

4-bp insertion/deletion (rs3783553) polymorphism within the 3'UTR of IL1A contributes to the risk of prostate cancer in a sample of Iranian population.

Growing evidence demonstrated the presence of an association between IL1A rs3783553 polymorphism and the risk of various cancers. We aimed to evaluate whether the 4-bp insertion/deletion polymorphism (rs3783553) within the 3' untranslated region (3'UTRs) of IL1A was associated to the risk of prostate cancer (PCa) in a sample of Iranian population. A case-control study, including 150 prostate cancer patients and 155 healthy men, was done to examine the possible association between IL1A 4-bp ins/del polymorphism and PCa risk in a sample of southeast Iranian population. Mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping the studied variant. Our findings showed that 4-bp ins/del polymorphism significantly increased the risk of PCa in codominant, recessive and allelic inheritance model. We also evaluated the association between the IL1A 4-bp ins/del polymorphism and clinicopathological characteristics of the patients, and found a significant association between 4-bp ins/del variant and stage, perineural invasion and surgical margin of tumor samples. Bioinformatics analysis revealed that the ins/del variant affected the IL1A mRNA stability leading to a structural shift in IL1A mRNA and has-miR-125a-3p hybrid. In conclusion, our findings proposed an association between IL1A 4-bp ins/del polymorphism and PCa risk. Additional studies with enlarged sample size and diverse ethnicities are required to validate our finding.

Evaluation of 4-bp insertion/deletion polymorphism within the 3'UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report.

The small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G-protein-coupled receptor signaling. There is little data regarding the impact of SGSM3 polymorphisms on cancer risk. In the present study, we aimed to evaluate the impact of 4-bp insertion/deletion (rs56228771) polymorphism in the 3'UTR of SGSM3 and susceptibility to bladder cancer in a sample of the Iranian population. This case-control study included 143 pathologically confirmed bladder cancer patients and 144 healthy subjects. The SGSM3 4-bp ins/del (rs56228771) variant was determined by mismatch PCR-RFLP. The findings showed that ins/del genotype and ins allele of SGSM3 4-bp ins/del polymorphism significantly increased the risk of bladder cancer (OR = 3.11, 95%CI = 1.70-5.71, P < 0.0001 and OR = 2.11, 95%CI = 1.27-3.52, P = 0.004, respectively). Our findings support an association between 4-bp ins/del polymorphism in the 3'UTR of SGSM3 and the risk of bladder cancer in an Iranian population. Additional studies with larger sample sizes and diverse ethnicities are warranted to establish if such an association exists in general.

Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population.

There is an increasing body of evidence which highlights the critical functions of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers. It has been reported that HOX transcript antisense intergenic RNA, a member of long non-coding RNA family, increases breast cancer risk. To date, no data regarding the association between HOX transcript antisense intergenic RNA polymorphisms and the risk of breast cancer development has been reported in Iran. Here, we examine the possible association between HOX transcript antisense intergenic RNA gene polymorphisms and breast cancer in a sample of southeast Iranian female population. The HOX transcript antisense intergenic RNA rs920778, rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases and 231 controls by polymerase chain reaction-restriction fragment length polymorphism. Our findings indicated that rs920778 polymorphism has significant positive association with breast cancer; rs12826786 and rs1899663 polymorphisms demonstrated significant negative association with breast cancer; and the rs4759314 variant was not associated with breast cancer risk. Haplotype analysis revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T haplotype. In conclusion, we investigated only four variants of HOX transcript antisense intergenic RNA gene, and the findings suggest that HOX transcript antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be associated with breast cancer risk in a sample of southeast Iranian population. Further replication studies with other polymorphisms of HOX transcript antisense intergenic RNA gene involving a greater sample size and different ethnicities are necessary to verify our findings.

IKZF1 gene polymorphisms increased the risk of childhood acute lymphoblastic leukemia in an Iranian population.

Genome-wide association studies (GWAS) have proved the association of IKZF1 polymorphisms with childhood acute lymphoblastic leukemia (ALL). In the present study, we aimed to inspect the impact of IKZF1 gene polymorphisms and childhood ALL in a sample of Iranian population who live in south east of Iran. This case-control study was done on 110 children diagnosed with ALL and 120 healthy children. The IKZF1 (rs4132601 T > G, rs11978267 A > G, rs11980379 T > C, and rs10272724 T > C) polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The results showed that rs4132601 T > G polymorphism increased the risk of ALL in the codominant (OR = 2.96, 95 % CI = 1.58-5.54, p = 0.0008, TG vs TT; and OR = 2.75, 95 % CI = 1.31-5.76, p = 0.0094, GG vs TT) and dominant (OR = 2.89, 95 % CI = 1.61-5.19, p = 0.0004, TG + GG vs TT) inheritance models. On the other hand, the rs4132601 G allele increased the risk of ALL (OR = 1.86, 95 % CI = 1.28-2.96; p = 0.0011) in comparison with the T allele. We have also showed that rs11980379 T > C variant increased the risk of ALL in codominant (OR = 2.43, 95 % CI = 1.28-4.60, p = 0.0076, TC vs TT; and OR = 2.35, 95 % CI = 1.14-4.85, p = 0.0291, CC vs TT) and dominant (OR = 2.40, 95 % CI = 1.32-4.36, p = 0.0038, TC + CC vs TT) inheritance models. The rs11980379 C allele increased the risk of ALL (OR = 1.59, 95 % CI = 1.10-2.31, p = 0.0151) compared with T allele. Our study also revealed that the rs10272724 T > C polymorphism increased the risk of ALL in codominant (OR = 2.18, 95 % CI = 1.19-3.99, p = 0.0115, TC vs TT; and OR = 2.67, 95 % CI = 1.24-5.77, p = 0.0131, CC vs TT) and dominant (OR = 2.31, 95 % CI = 1.30-4.08, p = 0.0049, TC + CC vs TT) inheritance models. On the one hand, the rs11980379 C allele increased the risk of ALL (OR = 1.70, 95 % CI = 1.17-2.46, p = 0.0062) compared with T allele, while the rs11978267 A/G polymorphism was not associated with ALL risk. In conclusion, our findings confirm the impact of IKZF1 polymorphisms on childhood ALL risk in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.

Lack of Association between rs4331426 Polymorphism in the Chr18q11.2 Locus and Pulmonary Tuberculosis in an Iranian Population.

OBJECTIVE: The effect of rs4331426 polymorphism in the Chr18q11.2 locus on pulmonary tuberculosis (PTB) risk was evaluated. METHODS: This case-control study included 208 PTB patients and 204 healthy subjects. Genotyping of the rs4331426 variant was conducted using polymerase chain reaction restriction fragment length polymorphism. RESULTS: The frequencies of genotypes AA, AG, and GG polymorphisms were 83.1%, 15.9%, and 1.0% in the PTB group and 84.3%, 15.2%, and 0.5% in the control group, respectively. The frequency of the minor (G) allele was 8.9% in the PTB group and 8.1% in controls. Neither genotype nor allele frequencies of the rs4331426 variant showed statistically significant differences between PTB and controls. In addition, stratification by sex showed no significant association between the rs4331426 variant and PTB risk in males or females. CONCLUSION: In conclusion, the results of this study do not support an association between the rs4331426 polymorphism and risk of PTB in an Iranian population.

Toll-like Receptor 1 Polymorphisms Increased the Risk of Pulmonary Tuberculosis in an Iranian Population Sample.

A case-control study was carried out that involved 203 individuals diagnosed with pulmonary tuberculosis (PTB) and 203 healthy subjects. Genotyping of TLR1 rs5743551 and rs5743618 polymorphisms was done using polymerase chain reaction-restriction fragments length polymorphism assay. We found that TLR1 rs5743551 variant affected the risk of PTB in the codominant (OR=3.28, 95% CI=1.98-5.45, P<0.0001, GA vs. GG; OR=1.86, 95% CI=1.05-3.28, P=0.033, AA vs. GG) and dominant (OR=2.69, 95% CI=1.67-4.34, P<0.0001, GA+AA vs. GG) inheritance models tested. The A allele was associated with a higher risk of PTB than the G allele (OR=1.33, 95% CI=1.01-1.75, P=0.049). The TG genotype of the rs5743618 variant significantly increased the risk of PTB compared to the risk associated with the TT genotype (OR=3.29, 95% CI=1.82-5.97, P<0.0001). The G allele was associated with a higher risk of PTB than the T allele (OR=3.00, 95% CI=1.69-5.31, P=0.0001). Our findings revealed that TLR1 rs5743551 and rs5743618 polymorphisms affected the risk of PTB in an Iranian population sample. Additional studies with larger sample sizes and involving subjects of different ethnicities are required to validate our present findings.

CCL5 rs2107538 Polymorphism Increased the Risk of Tuberculosis in a Sample of Iranian Population.

Cysteine-cysteine chemokine ligand 5 (CCL5) with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5) is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 -403G/A (rs2107538), CCL5 -28C/G (rs2280788) and CCR5 Δ32 polymorphisms and pulmonary tuberculosis (PTB) in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 -403G/A, CCL5 -28C/G and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR), tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 -403G/A (rs2107538) increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03-2.81, P=0.038 and OR=1.64, 95% CI=1.00-2.68, P=0.049, respectively). No significant association was found between CCL5 -28C/G as well as CCR5 Δ32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 -403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings.

Association between Mir-499, Mir-27a, and Mir-146a polymorphisms and their susceptibility to recurrent spontaneous abortion; in silico analysis.

Objective: Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy losses before 24 gestational weeks, accounting for 1-3% of fertile couples. A vast majority of single-nucleotide polymorphisms (SNPs) in some microRNA (miRNA) genes can change the miRNA-mRNA interaction and are associated with the risk of RSA. This study was designed to better elucidate the association between miR-27a, miR-499, and miR-146a polymorphisms and RSA risk. Materials and Methods: SNP genotyping of miR-27a (rs895819), miR-499 (rs3746444), and miR-146a (rs2910164) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification-refractory mutation system PCR in 98 patients with RSA and 105 healthy subjects. Results: Our results showed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were significantly associated with RSA risk, whereas no significant differences were observed between the rs2910164 polymorphism and RSA susceptibility. Conclusion: We proposed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were correlated with RSA in our population, but the miR-146a rs2910164 variant was not associated with the risk of RSA.

Association of LIN28B Gene Polymorphisms (rs221634, rs221635, rs314276, rs9404590, and rs12194974) with Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND AND AIM: Lymphoma is a common hematopoietic cancer.  It has been proposed that LIN28B gene and its variations may have function in cancer progression and metastasis. Therefore, the purpose of this investigation has been to examine the correlation among LIN28B gene polymorphisms (such as rs221634 A>T, rs221635 T> C, rs314276 C>A, rs9404590 T>G, and rs12194974 G>A) as well as the risk of NHL in an Iranian sample. MATERIALS AND METHODS: In the current case-control research, 175 individuals with Non-Hodgkin Lymphoma along with 175 normal controls participated; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology has been utilized to the genotype samples. RESULTS: Our data demonstrated that rs12194974 and the rs221635 variants have been correlated with higher NHL risk, while rs221634 and rs314276 variants were correlated with lower risk of NHL (P≤0.05). In addition, we detected an association between rs221634 and treatment with R-CHOP. No substantial correlation has discovered among rs9404590 polymorphism and NHL in any inheritance models (P≥0.05). CONCLUSION: This was the first investigation evaluating the correlation among LIN28B gene polymorphisms as well as the occurrence of NLH. Further studies in different ethnic populations and large-scale sample size are needed to support results.

The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case-Control Study with Bioinformatics Analysis.

Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer development, with genetic variations affecting its function. We investigated the rs34917480 in RTN4 and its association with BC risk in an Iranian population sample. We also predicted the rs34917480 effect on RTN4 mRNA structure and explored the RTN4's protein-protein interaction network (PPIN) and related pathways. In this case-control study, 437 women (212 BC and 225 healthy) were recruited. The rs34917480 was genotyped using AS-PCR, mRNA secondary structure was predicted with RNAfold, and PPIN was constructed using the STRING database. Our findings revealed that this variant was associated with a decreased risk of BC in heterozygous (p = 0.012), dominant (p = 0.015), over-dominant (p = 0.017), and allelic (p = 0.035) models. Our prediction model showed that this variant could modify RTN4's mRNA thermodynamics and potentially its translation. RTN4's PPIN also revealed a strong association with apoptosis regulation and key signaling pathways highly implicated in BC. Consequently, our findings, for the first time, demonstrate that rs34917480 could be a protective factor against BC in our cohort, probably via preceding mechanisms.

Association of IRGM polymorphisms and susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran.

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions -1208 A/G (rs4958842), -1161 C/T (rs4958843), and -947 C/T (rs4958846) were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR). The results showed that the IRGM -1161 C/T and -947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03-0.13, P < 0.001 and OR = 0.27; 95% CI = 0.013-0.55, P < 0.001, resp.). No significant difference was found among the groups regarding -1208 A/G polymorphism. In conclusion we found that the IRGM -1161 C/T and -947 C/T polymorphisms but not -1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.

Association between PAX8AS1 (rs4848320 C > T, rs1110839 G > T, and rs6726151 T > G) and MEG3 (rs7158663) gene polymorphisms and non-Hodgkin lymphoma risk.

Long non-coding RNA (lncRNA) PAX8 antisense RNA 1 (PAX8AS1) and Maternal-expressed gene 3 (MEG3) contribute to the pathogenesis of various malignancies including non-Hodgkin lymphoma (NHL). In this study, we aimed to examine the possible association of polymorphisms of PAX8 and MEG3 and the risk NHL. A total of 175 patients and 175 healthy subjects were genotyped by PCR-RFLP and Tetra-Arms PCR assays. Results demonstrated rs4848320 C > T and rs6726151 T > G of PAX8AS1 and rs7158663 of MEG3 play a potential role in the susceptibility of NHL and PAX8AS1 rs1110839 T > G variant was associated with decreased risk of NHL. Haplotype analysis of rs1110839, rs4848320, and rs6726151 demonstrated GCG haplotype is associated with increased risk of lymphoma and TTG, TTT, and GTT haplotypes are related to decreased lymphoma susceptibility.

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND: Caspases (CASPs) are the main executors of the apoptotic process. Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. Therefore, the aim of this study was to investigate the associations between CASP9-rs4233532, CASP9-rs4646018, and CASP8- rs1045485 gene polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility in an Iranian population-based study. Moreover, it was examined whether such the genotype of these polymorphisms is related with clinicopathological characteristics of NHL. METHODS: 175 patients with NHL and 175 age- and sex-matched controls were enrolled in this study. We determined the genotypes of single nucleotide polymorphisms (SNPs) from CASP genes with Tetra ARMS-PCR (Amplification refractory mutation system) method. RESULTS: Statistically significant association were observed between CASP9-rs4646018 and increased risk of NHL under codominant CC, codominant TC, and dominant TC+CC genetic models. Our results showed that the A allele of CASP8-rs1045485 was a protective factor for NHL and GArs1045485 genotype significantly reduced risk of NHL. In contrast, CASP9- rs4233532 was not linked to NHL susceptibility. No relationship was detected between CASP8-rs1045485 and CASP9-rs4233532 and NHL clinicopathological characteristics, however genetic variation in CASP9-rs4646018 was associated with histology, treatment and radio therapy of NHL. CONCLUSIONS: Our study presented that the CASP8- rs1045485 and CASP9-rs4646018 polymorphisms could affect the risk of NHL in Iranian populations which was the first report to show the significant relationship between rs1045485, rs4646018 polymorphisms and NHL susceptibility. Replication large-scale case-control studies in different ethnicities are warranted to verify these findings.