Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism Is Associated with Increased Risk of Nephrotic Syndrome in Children.

INTRODUCTION: Nephrotic syndrome (NS), a common chronic pediatrickidney disease, is associated with immune system dysfunction.The exact role of MIF -137 G>C gene polymorphism on risk of NSis not clear. The current study aimed to evaluate the relationshipbetween MIF -173 G>C (rs755622) variant and susceptibility to NS. METHODS: This case-control study conducted on 134 children withNS and 141 healthy children. Extraction of genomic DNA fromwhole blood was done using salting out method. Genotyping ofthe MIF -173 G>C polymorphism was performed using polymerasechain reaction restriction fragment length polymorphism (PCRRFLP)method. RESULTS: The findings showed that MIF -173 G>C variant significantlyincreases the risk of NS in codominant (OR = 1.82, 95%CI = 1.08-3.08, P = 0.026, GC vs GG), dominant (OR = 1.90, 95%CI = 1.14-3.16,P = 0.015, GC+CC vs GG), overdominant (OR = 1.75, 95%CI = 1.04-2.94, P = 0.037, GC vs GG+CC) and allele (OR = 1.76, 95%CI = 1.13-2.74, P = 0.014, C vs G) inheritance models. Stratified analysisperformed by sex and response to treatment. The findings revealedthat this variant was associated with increased risk of NS in male.No correlation between the variant and response to treatment wasfound. CONCLUSION: In summary, the results indicated that MIF -137 G>Cis significantly associated with increased risk of NS. More studieswith larger sample size among different ethnicities are needed toverify our findings.

Association between genetic variants in CD1A and CD1D genes and pulmonary tuberculosis in an Iranian population.

Cluster of differentiation (CD)1 molecules are a highly conserved family of MCH-like transmembrane glycoproteins that bind lipid and glycolipid antigens and present a diverse range of microbial and self-glycolipids to antigen-specific T cells. The current study aimed to find out the impact of CD1A and CD1D polymorphisms on pulmonary tuberculosis (PTB). This case-control study encompassed 172 PTB patients and 180 healthy subjects. Genotyping of CD1A and CD1D variants was achieved using the polymerase chain reaction restriction fragment length polymorphism method. The results revealed that CD1A rs411089 variant significantly increased the risk of PTB in recessive model [odds ratio (OR)=2.71, 95% confidence interval (CI)=1.38-5.57, CC vs. TT+TC, P=0.005]. CD1D rs859009 polymorphism significantly reduced the risk of PTB in heterozygous codominant (OR=0.50, 95% CI=0.29-0.86, P=0.011, GC vs. GG) and dominant (OR=0.53, 95% CI=0.31-0.88, P=0.019, GC+CC vs. GG) inheritance model. The CD1A rs366316, CD1D rs973742 and CD1D rs859010 were not associated with the risk/protection from PTB (P>0.05). The results of the present study suggest that CD1A rs411089 and CD1D rs859009 but not CD1A rs366316, CD1D rs973742 and CD1D rs859010 polymorphisms are associated with PTB in a sample of the Iranian population. Further investigation with different ethnicities and larger sample sizes are necessary to certify the findings of the present study.

Association between Pri-miR-34b/c rs4938723 polymorphism and bladder cancer risk.

Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This study aimed to assess possible association between rs4938723 polymorphism and bladder cancer risk. This case-control study was done on 136 pathologically proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c rs4938723 polymorphism was achieved by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Our findings did not show any statistically significant differences in genotype and allele frequencies between bladder cancer and controls. Larger sample sizes with diverse ethnicities are required to validate our findings.

Detection of a 4-bp Insertion/deletion Polymorphism within the Promoter of EGLN2 Using Mismatch PCR-RFLP and Its Association with Susceptibility to Breast Cancer

It has been shown that a 4-bp insertion/deletion (ins/del) polymorphism of EGLN2 influences the risk of several cancers. However, to date, no study has inspected the impact of the 4-bp ins/del polymorphism on breast cancer (BC) risk. A case-control study, including 134 breast cancer patients and 154 healthy women, was here conducted to examine the possible association between EGLN2 4-bp ins/del polymorphism and BC risk in a southeast Iranian population. A mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping of the variant. Our findings did not support any association between the 4-bp ins/del polymorphism and the risk of BC in the codominant, dominant, recessive and allele inheritance models tested. When links between the EGLN2 4-bp ins/del polymorphism and clinicopathological characteristics of the patients were evaluate the variant was only associated with HER2 status. More studies with larger sample sizes and diverse ethnicities are warranted to verify 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.

The -2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is a common health problem affecting women of reproductive age. Altered expression of vascular endothelial growth factor (VEGF) has been associated with spontaneous abortion. The present case-control study aimed to evaluate the impact of the 18-bp insertion/deletion (ins/del) polymorphism (rs35569394) in the promoter region of the VEGF gene on idiopathic RSA. Genomic DNA from 93 patients with RSA and 93 healthy fertile women of southeastern Iran was isolated using the salting-out method. Genotyping of the rs35569394 variant was performed by a polymerase chain reaction (PCR) method. The findings indicated that the VEGF 18-bp ins/del variant significantly increased the risk of RSA under codominant (ins/ins vs. del/del; OR=2.85, 95% CI=1.31-6.22, P=0.019), dominant (del/ins+ins/ins vs. del/del; OR=2.19, 95% CI=1.20-4.01, P=0.015) and allelic (ins vs. del; OR=1.90, 95% CI=1.25-2.88, P=0.003) inheritance models. In summary, the findings propose a significant association between the VEGF 18-bp ins/del polymorphism and risk of RSA in a sample of the southeast Iranian population. Further studies on larger sample sizes and different ethnicities are required to validate the present findings.

Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion.

It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA. Impact statement What is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population. What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population. What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities on the role of TCN2 and TCN2R polymorphisms in the pathogenesis of RSA.

Association between single nucleotide polymorphisms in the PI3K/AKT/mTOR pathway and bladder cancer risk in a sample of Iranian population.

In the past few years several investigations have focused on the role of PI3K/AKT/mTOR pathway and its deregulations in different cancers. This study aimed to examine genetic polymorphisms of this pathway in bladder cancer (BC). In this case-control study, 235 patients with pathologically confirmed bladder cancer and 254 control subjects were examined. PIK3CA, AKT1 and mTOR variants were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The findings proposed that the PIK3CA rs6443624 SNP significantly decreased the risk of BC (OR=0.44, 95 % CI=0.30-0.65, p<0.0001 CA vs CC; OR=0.35, 95 % CI=0.16-0.78, p=0.0107, AA vs CC; OR=0.60, 95 % CI=0.46-0.79, p=0.0002, A vs T). The AKT1 rs2498801 variant is associated with a decreased risk of BC (OR=0.57, 95 % CI=0.39-0.82, p=0.003, AG vs AA; OR=0.74, 95 % CI=0.56-0.97, p=0.032, G vs A) while, AKT1 rs1130233 polymorphism considerably increased the risk of BC (OR=3.70, 95 % CI=2.52-5.43, p<0.0001, GA vs GG; OR=5.81, 95 % CI=1.53-21.97, p=0.010, AA vs GG; OR=2.71, 95 % CI=1.98-3.70, p<0.0001, A vs G). Additionally, mTOR rs2295080 variant notably increased the risk of BC (OR=2.25, 95 % CI=1.50-3.38, p<0.0001, GT vs GG; OR=4.75, 95 % CI=2.80-8.06, p<0.0001, TT vs GG; OR=3.10, 95 % CI=2.34-4.10, p<0.0001, T vs G). None of the other examined polymorphisms (AKT1 rs1130214, AKT1 rs3730358, mTOR rs1883965) revealed significant association with BC. In conclusion, our findings suggest that PIK3CA rs6443624, AKT1 rs2498801, AKT1 rs1130233, as well mTOR rs2295080 polymorphism may be related to bladder cancer development in a sample of Iranian population. Validation of our findings in larger sample sizes of different ethnicities would provide evidence on the role of variants of PI3K/AKT/mTOR pathway in developing BC.

Association study of miR-100, miR-124-1, miR-218-2, miR-301b, miR-605, and miR-4293 polymorphisms and the risk of breast cancer in a sample of Iranian population.

MicroRNAs (miRNAs) regulate genes expression by directly binding to the 3' untranslated region (3'UTR) of specific target mRNAs. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are proposed to be important in the development of breast cancer (BC). In the present study, we conducted a case-control study with 266 BCE patients and 288 control women to examine the possible association of miRNAs polymorphisms (miR-100 rs1834306, miR-124-1 rs531564, miR-218-2 rs11134527, miR-301b rs384262, miR-605 rs2043556, and miR-4293 rs12220909) with BC susceptibility. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The findings showed miR-218-2 rs11134527 variant increased the risk of BC (OR = 7.70, 95%CI = 3.84-15.43, P < .0001, GA vs GG and OR = 6.86, 95%CI = 3.47-13.57, P < .0001, A vs G). Regarding miR-301b rs384262 polymorphism, we observed that this variant significantly increased the risk of BC (OR = 3.12, 95%CI = 2.20-4.45, P < .0001, AG vs AA and OR = 2.22, 95%CI = 1.68-2.93, P < .0001, G vs A). Our findings did not support an association between miR-100 rs1834306, miR-124-1 rs531564, miR-605 rs2043556 and miR-4293 rs12220909 polymorphism and the risk of BC. In conclusion, the finding showed that miR-218-2 rs11134527 and miR-301b rs384262 variant might contribute to increase the risk of BC in a sample of Iranian population. Additional studies with larger sample sizes and different ethnicities are necessary to confirm our finding.

Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population.

OBJECTIVES: Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. MATERIAL AND METHODS: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. CONCLUSION: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

Pri-miR-34b/c rs4938723 polymorphism increased the risk of prostate cancer.

The association studies between miR-34b/c rs4938723 polymorphism and cancer risk showed conflicting results. This study aimed to assess the impact of rs4938723 polymorphism on prostate cancer risk. This case-control study was done on 151 prostate cancer (PCa) patients and 152 benign prostate hyperplasia to examine whether rs4938723 polymorphism in the promoter of pri-miR-34b/c was linked to the carcinogenesis of PCa in a sample of Iranian population. Genotyping of Pri-miR-34 b/c rs4938723 polymorphism was performed by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The results showed that rs4938723 variant significantly increased the risk of PCa in codominant (OR = 1.92, 95% CI = 1.15 - 3.18, p= 0.012, TC vs TT), dominant (OR = 1.99, 95% CI = 1.23 - 3.24, p= 0.005, TC + CC vs TT), and allelic (OR = 1.79, 95% CI = 1.20 - 2.68, p= 0.005, C vs T) inheritance model. Our findings propose that Pri-miR-34 b/c rs4938723 variant may be a risk factor for the development of PCa in a sample of Iranian population. Larger sample sizes with different ethnicities are required to validate our findings.