Polymorphism of the DNA repair gene XDP increases the risk of systemic lupus erythematosus but not multiple sclerosis in the Iranian population.

BACKGROUND: Xeroderma pigmentosum group D ( XPD ) is an essential component of the nucleotide excision repair (NER) pathway, which can play a major role in DNA repair processes. A deficiency in this pathway was suggested as a causative factor of autoimmune diseases. Therefore, the current study aimed to investigate the relationship between XPD Lys751Gln polymorphism (rs13181) as one of the most common XDP polymorphisms and the risk of two important auto-immune diseases,namely systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the Iranian population. METHODS: 165 SLE patients and 165 age- and gender-matched healthy controls, and 150 MS patients and 150 age- and gender-matched healthy controls were genotyped for XPD rs13181 A/C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The results of the present study have indicated that both C allele frequency ( P = 0.012; odds ratio: 1.5; 95% confidence interval: 1.1-2.07) and CC genotype ( P = 0.007; odds ratio: 2.46; 95% confidence interval: 1.2-4.7) in SLE patient were significantly higher than those in control group. Furthermore, there were no significant differences between MS patients and normal subjects concerning the genotype and the allele frequencies. CONCLUSION: Our findings suggested that XPD rs13181 A/C polymorphism may be a crucial risk factor for the development of SLE but not MS in Iranian patients.

Effects of the MTOR and AKT1 genes polymorphisms on papillary thyroid cancer development.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer, comprising 80% of all thyroid malignancies. The phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-PKB/Akt) pathway is a main pathway in control of cell growth. Activated mTOR and Akt are involved in the development and progression of the PTC. This study aimed to evaluate the effects of MTOR (rs2536 and rs2295080) and AKT1 (rs2494732, rs1130214, and rs1130233) polymorphisms on PTC susceptibility. This study was conducted on 131 PTC patients and 144 healthy subjects. Genotype analysis was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Our results showed no statistically significant association between MTOR rs2536, AKT1 rs2494732, and rs1130214 polymorphisms and PTC development. However, MTOR rs2295080 polymorphism was found to be associated with a decreased risk of PTC in dominant and allelic models. The TT genotype of AKT1 rs1130233 was significantly higher in the PTC group in comparison to the controls, with a 3.5-fold increased risk for developing PTC. Furthermore, the allelic distribution also showed the T allele of rs1130233 as a risk factor for PTC occurrence. In conclusion, our results suggest the MTOR rs2295080 and AkT1 rs1130233 as the protective and risk factors for PTC development, respectively.

Effects of the mTOR and AKT genes polymorphisms on systemic lupus erythematosus risk.

The systemic lupus erythematosus (SLE) is an autoimmune disease, leading to inflammatory response and systemic consequences. The mammalian target of rapamycin (mTOR) is a therapeutic target for autoimmune diseases like SLE. The aim of this study was to evaluate the effects of the mTOR rs2295080 and rs2536 polymorphisms and AKT1 rs2494732 gene polymorphism on SLE development. 2 ml of peripheral blood was collected from 165 SLE patients and 170 controls in EDTA-containing tubes. The salting-out and PCR-RFLP methods were used for DNA extraction and genotype analysis, respectively. Based on the regression analysis, the frequency of TT genotype of mTOR rs2295080 polymorphism was significantly higher in the case group than that of the control group, with a 2.6-fold increased risk of SLE. There was also a significant difference between the two groups in terms of allelic distribution. No statistically significant association was found between The AKT1 rs2494732 and mTOR rs2536 polymorphisms and SLE development. Our results showed that the TT genotype and T allele of mTOR rs2295080 polymorphism were risk factors for developing SLE. However, there was no significant association between mTOR rs2536 and AKT1 rs2494732 polymorphisms and the SLE risk.

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features.

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic polymorphisms of the TP53 and P21 genes are the candidate variants in various cancers development. This study investigated whether the polymorphisms in TP53 (rs1042522) and P21 (rs1059234 and rs1801270) affect the risk of PTC and whether such the genotype of these polymorphisms is associated with pathological and clinical characteristics of PTC. A case-control study was conducted with 286 Iranian people, including 131 PTC cases and 155 healthy controls. The genetic polymorphisms were investigated by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results suggested that TP53-rs1042522 CC genotype was significantly associated with protection against PTC, in the dominant, recessive and allelic models (OR = 0.4, 95%CI: 0.2-0.8, P = .008; OR = 0.5, 95%CI: 0.3-0.9, P = .01; OR = 0.6, 95%CI: 0.4-0.8, P = .002, respectively). The rs1042522 was associated with PTC patients with tumor size greater than 1 cm in dominant and recessive models (OR = 0.2, 95%CI = 0.04-0.9, P = .04 and OR = 0.3, 95%CI = 0.1-0.7, P = .009, respectively) and was associated with vascular invasion in dominant model (OR = 0.3, 95%CI = 0.1-0.7, P = .01). No correlation was identified between P21 rs1059234 and rs1801270 polymorphisms and risk of PTC and pathological and clinical characteristics of PTC. Genetic variations in rs1042522 might alter the PTC risk, which could affect tumor size and cause lower incidence of vascular invasion in PTC cases. This was the first report suggesting that no correlation was found between P21 rs1059234 and rs1801270 polymorphisms and PTC risk. Thus, more studies with a larger population size and different ethnic groups and functional assays are needed to confirm our results.

The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious problem in pregnancy. The exact etiology of RSA is unknown in more than 50% of all the patients. However, genetic variations are known as susceptibility factors for idiopathic RSA. Considering the role of miRNA biosynthesis machinery in the miRNA production and effect of miRNAs on various diseases, this study aimed to evaluate the effects of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms on RSA risk. METHODS: In this case-control study, 150 RSA patients and 195 age-matched healthy female controls were recruited. Both polymorphisms were genotyped using PCR-RFLP method. RESULTS: The frequency of DICER1 rs3742330AG genotype was higher in the control group (P = .022). There was a statistically significant association between rs3742330 polymorphism and a reduced RSA risk in dominant and allelic models (P = .013 and P = .007, respectively). No statistically significant association was found between DROSHA rs6877842 variant and RSA risk. The combination of AG and GC genotypes and G-G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms led to a decreased RSA risk. However, the synergic effect of rs3742330A and rs6877842G alleles (A-G) and AA-GG genotypes was associated with an increased RSA risk. CONCLUSION: the DICER1 rs3742330AG genotype and combination of AG and GC genotypes and G-G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms were associated with a reduced RSA risk.

Role of MDM2 309T>G (rs2279744) and I/D (rs3730485) polymorphisms and haplotypes in risk of papillary thyroid carcinoma, tumor stage, tumor size, and early onset of tumor: A case control study.

Murine double minute clone 2 (MDM2) protein plays an important role in the regulation of p53 tumor suppressor. Genetic polymorphisms of the MDM2 gene are the candidate variants in susceptibility to various cancers. In the present study, we aimed to investigate the possible effects of MDM2 309T>G (rs2279744) and I/D (rs3730485) polymorphisms on papillary thyroid carcinoma (PTC) susceptibility and clinical or pathological features of the disease. A case control study was carried out involving in a total of 131 patients with PTC and 144 healthy controls. Both cases and controls were genotyped for MDM2 309T>G and I/D polymorphisms. There was no significant difference regarding MDM2 309T>G and I/D genotypes between patients with PTC and controls in neither dominant nor recessive and allelic models. The frequency of G-D haplotype was higher in patients with PTC and this haplotype was associated with a 1.7-fold increased risk of PTC. The MDM2 309T>G polymorphism was associated with a higher risk of III-IV stages in patients with PTC. The MDM2 ID genotype was significantly higher in patients with PTC less than 40 years and associated with larger tumor size (≥1 cm). In conclusion, the G-D haplotype but not MDM2 309T>G and I/D polymorphisms were associated with higher risk of PTC. MDM2 309T>G polymorphism was associated with a higher incidence of III-IV stages, however, I/D polymorphism was associated with larger tumor size and a lower age of disease occurrence.