Majid Naderi

R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran.

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran.

Susceptibility to tuberculosis may be influenced by variations in human genes. The P2X7 receptor is an ATP-gated cation channel expressed in immune cells, and it influences the release of proinflammatory cytokines from monocytes and macrophages. In the present study, we aimed to evaluate the impact of P2X7 gene rs2393799 (-762T/C) and rs1718119 (Thr348Ala) polymorphisms on patient susceptibility to pulmonary tuberculosis (PTB) in a sample of the Iranian population. This case-control study was performed using 150 PTB cases and 150 controls. P2X7 receptor polymorphisms were determined using tetra-amplification refractory mutation system-polymerase chain reaction. Genotype and allelic frequencies of the rs2393799 variant within the P2X7 gene were significantly higher in the PTB patients than in the healthy controls. The genotypes were CC in 71, CT in 54, and TT in 25 PTB patients. The genotypes were CC in 104, CT in 40, and TT in 6 healthy controls. The results indicate a significant association between rs2393799 polymorphism of the P2X7 gene and susceptibility to PTB (CT vs CC: OR = 6.5, 95%CI = 2.5-16.9, P < 0.0001; TT vs CC: OR = 3.3, 95%CI = 1.2-8.9, P = 0.018; TC+TT vs CC: OR = 2.56, 95%CI = 1.59-4.12, P < 0.0001). The rs2393799 T allele is a risk factor for predisposition to PTB (OR = 2.53, 95%CI = 1.73-3.71, P < 0.0001). No association between the rs1718119 polymorphism and PTB was found. In conclusion, the rs2393799 polymorphism in the P2X7 gene may contribute to patient susceptibility to PTB in our study population.

Lack of Association between Interleukin-18 -607 C/A Gene Polymorphism and Pulmonary Tuberculosis in Zahedan, Southeast Iran

Interleukin-18 (IL-18) plays a critical role in immune response, contributing to the pathogenesis and pathophysiology of infectious diseases. Polymorphisms in the IL-18 genes are known to influence expression levels and may be associated with outcome of infections. The objective of this study was to determine whether the presence of IL-18 polymorphisms -607 A/C (rs1946518) was associated with tuberculosis disease. We investigated the functional polymorphism of IL-18 (rs1946518) in 174 patients with pulmonary tuberculosis (PTB) and 177 healthy subjects. Genotype analysis was done using tetra amplification refractory mutation system-PCR (T-ARMS-PCR). The allelic and genotypic frequencies of the IL-18 polymorphism did not differ significantly between PTB and the controls. Our finding suggests that IL-18 polymorphism (rs1946518) may not be a risk factor for susceptibility to tuberculosis in a sample of Iranian population. Further studies are required to validate our findings.

Pri-miR-34b/c rs4938723 polymorphism is associated with the risk of childhood acute lymphoblastic leukemia

MicroRNAs (miRNAs), small noncoding regulatory RNAs, are key regulators of gene expression. The impact of Pri-miR-34b/c rs4938723 variant on development of various cancers is still controversial. In the present study, we examined whether a rs4938723 variant located at the promoter region of Pri-miR-34b/c is associated with childhood ALL. A total of 110 children with acute lymphoblastic leukemia (ALL) and 120 healthy children were recruited to participate in this study. The rs4938723 variant was genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The rs4938723 variant decreased the risk of ALL in heterozygous (TC vs OR = 0.48, 95% CI = 0.28-0.84, p = 0.012, TC vs TT) and overdominant (OR = 0.51, 95% CI = 0.30-0.89, p = 0.0.020, TC vs TT + CC): OR = 1.32, 95% CI = 0.67-2.59, p = 0.498; C vs T: OR = 0.99, 95% CI = 0.75-1.31, p = 0.986) inheritance models tested. The C allele significantly decreased the risk of childhood ALL compared to T allele (OR = 0.52, 95% CI = 0.33-0.83, p = 0.006). Our findings proposed an association between Pri-miR-34 b/c rs4938723 variant and risk of childhood ALL development in a sample of Iranian population.

Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia

Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.

Lipid profile in patients with psoriasis in Zahedan, south‐east Iran

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Long non‑coding RNA PAX8‑AS1 polymorphisms increase the risk of childhood acute lymphoblastic leukemia

The present case-control study was conducted on 110 children with acute lymphoblastic leukemia (ALL) and 120 healthy children to determine the impact of polymorphisms in paired-box gene 8 (PAX8) antisense RNA 1 (PAX8-AS1), namely rs4848320 C>T, rs6726151 T>G and rs1110839 G>T, on ALL risk. Genotyping was performed through the polymerase chain reaction-restriction fragment length polymorphism method. The findings indicated that the rs4848320 variant increased the risk of ALL in codominant [CT vs. CC: odds ratio (OR)=2.13, 95% confidence interval (CI)=1.16-3.90, P=0.014; and TT vs. CC: OR=2.21, 95% CI=1.03-4.74, P=0.041], dominant (CT+TT vs. CC: OR=2.15, 95% CI=1.22-3.81, P=0.009,) and allele (T vs. C: OR=1.55, 95% CI=1.07-2.25, P=0.024) inheritance models. The rs6726151 variant significantly increased the risk of ALL in codominant (GT vs. GG: OR=1.88, 95% CI=1.08-3.27, P=0.036) and overdominant (GT vs. GG+TT: OR=2.08, 95% CI=1.23-3.53, P=0.008) inheritance models. No significant relationship was identified between the rs1110839 G>T variant and disease risk/protection in childhood ALL. In conclusion, the findings of the present study indicated that rs4848320 and rs6726151 polymorphisms of PAX8-AS1 may be a risk factor for the development of childhood ALL. Further studies with larger sample sizes and different ethnicities are now required to confirm these findings.

Leukocyte Telomere Length Shortening, hTERT Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia

Background: Telomeres are involved in chromosomal stability, cellular immortality and tumorigenesis. Human telomerase reverse transcriptase (TERT) is essential for the maintenance of telomere DNA length. Recently, a variable tandem-repeats polymorphism, MNS16A, located in the downstream region of the TERT gene, was reported to have an effect on TERT expression and telomerase activity. Previous studies have linked both relative telomere length (RTL) and TERT variants with cancer. Therefore, we evaluated associations between RTL, TERT gene polymorphisms (hTERT, rs2735940 C/T and MNS16A Ins/Del) and risk of childhood acute lymphoblastic leukemia (ALL) in an Iranian population. Methods: RTL was determined by a multiplex quantitative PCR-based method, and variants of the hTERT, rs2735940 C/T and MNS16A Ins/Del, were genotyped by amplification refractory mutation system PCR (ARMS-PCR), and PCR, respectively. Results: Our results indicated that RTL was shorter in ALL patients (1.53±0.12) compared to the control group (2.04±0.19) (P=0.029). However, no associations between hTERT gene variants or haplotypes and the risk of childhood ALL were observed (P>0.05). Also hTERT polymorphisms were not associated with RTL or patient clinicopathological characteristics, including age (P=0.304), sex (P=0.061) organomegally (P=0.212) CSF involvement (P=0.966) or response to treatment (P=0.58). Conclusions: We found that telomere attrition may be related to the pathogenesis of childhood ALL, irrespective to TERT variants.

FHIT promoter DNA methylation and expression analysis in childhood acute lymphoblastic leukemia

Fragile histidine triad (FHIT) is a tumor suppressor gene, which is involved in several malignancies. Epigenetic alterations in FHIT have been hypothesized to contribute to tumorigenesis. The present study aimed to examine DNA promoter methylation and gene expression levels of FHIT in childhood acute lymphoblastic leukemia (ALL), in a sample of Iranian patients. The promoter methylation status of FHIT was analyzed in 100 patients diagnosed with ALL and 120 healthy control patients. mRNA expression levels were assessed in 30 new cases of ALL compared with 32 healthy controls. Hypermethylation of the FHIT promoter was significantly more frequent in patients with ALL than in healthy controls (OR=3.83, 95% CI=1.51-9.75, P=0.007). Furthermore, FHIT mRNA expression levels were significantly reduced in childhood ALL patients compared with healthy controls (P=0.032). The results of the present study revealed that dysregulation of the FHIT gene may contribute to the pathogenesis of childhood ALL. Future studies investigating a larger sample population with greater ethnic diversity would be beneficial, to confirm the results from the present study.

Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia—A case-control study from Iran

ABSTRACT We examined the possible relationship between three RAGE polymorphisms, −429C/T, −374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE −374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.