Our findings demonstrated that the hsa-mir-499 rs3746444 polymorphism is associated with higher risk of developing breast cancer in our population.
Growing evidence showed that microRNAs (miRs) are involved in normal hematopoiesis and the pathogenesis of several hematological malignancies. Genetic variations or mutations occurring in the miR gene region may affect the property of miRs through altering miR expression and/or maturation. The aim of the present study was to evaluate the possible relationship between two miRs polymorphisms, hsa-miR-146a (rs2910164 G>C) and hsa-miR-499 (rs3746444 T>C), and the susceptibility to childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. This case-control study was performed on 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group). Tetra-primer amplification refractory mutation system-polymerase chain reaction was applied for genotyping the variants. We found that the rs2910164 G>C variant of hsa-miR-146a significantly increased the risk of ALL (CC vs. GG, OR = 4.24, 95% CI = 1.52-11.87, P = 0.006; GC vs. GG, OR = 3.55, 95% CI = 1.41-8.93, P = 0.007; C vs. T, OR = 1.73, 95% CI = 1.13-2.67, P = 0.012). With respect to hsa-miR-499 rs3746444 T/C, no significant difference in allele and genotype frequencies of the rs3746444 variant between ALL patients and controls was observed. Our results for the first time demonstrated that the miR-146a rs2910164, but not miR-499 rs3746444 variant, was associated with increased risk for developing pediatrics ALL in an Iranian population.
Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that is highly expressed in cancer pathologies. A 14-bp insertion/deletion polymorphism in exon 8 of the 3' untranslated region (3'-UTR) of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. This study aimed to evaluate the association of 14-bp ins/del polymorphism in HLA-G gene and breast cancer in a south-east Iranian population. This study was performed using 236 patients with breast cancer and 203 healthy subjects. We designed a rapid and simple bi-directional PCR allele-specific amplification (Bi-PASA) for detection of 14-bp ins/del polymorphism in the HLA-G gene. The results of our study revealed that the prevalence of HLA-G 14-bp homozygote deletion genotype was higher in breast cancer patients than in the control group (OR=2.06, 95%CI=1.23-3.44, P=0.006). The frequency of the Del allele was 56.4% in breast cancer patients and 46.5% in the control group and the difference was statistically significant (OR=1.48, 95%CI=1.13-1.94, P=0.004). Moreover we evaluated the possible correlation of the HLA-G 14-bp ins/del genotypes and clinical characteristics of the patients, but no statistically significant correlation was found (P> 0.05). Our findings, for the first time, suggest that the 14-bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma. Further studies on larger populations with different ethnicities are required to verify our findings.
Interferon-gamma (IFN-g) is a pro-inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN-g in (þ874 A/T in intron 1) TT and þ5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-g variants by an allele-specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the þ874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR ¼ 2.588; 95% CI, 1.313-5.104; P ¼ 0.006 for the AA genotype; OR ¼ 1.575; 95% CI, 1.124-2.216; P ¼ 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN-g polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (þ874/ UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN-g þ874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.
Introduction:It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL).Materials and Methods:We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction.Results:We found that DROSHA rs642321 C > T variant significantly decreased the risk of ALL in codominant (TT vs. CC: odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.14–0.80, P = 0.020) and dominant (TT + CT vs. CC: OR = 0.51, 95% CI = 0.27–0.94, P = 0.037) inheritance model tested. The rs642321 T allele was associated with protective against ALL (OR = 0.58, 95% CI = 0.38–0.88, P = 0.011) in comparison with C allele.Conclusion:The study findings revealed that DROSHA rs642321 variant decreased the risk of pediatrics ALL in an Iranian population. Larger sample sizes with different ethnicities are needed to validate our findings.
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