Personalized and Precision Medicine Journal

Abstract Background: Matrix metalloproteinases (MMPs) play a critical role in tumor invasion and metastasis in papillary thyroid carcinoma (PTC). This study investigates the association of MMP2 (rs7201) and MMP9 (rs17576) polymorphisms with PTC risk and clinical characteristics, aiming to inform personalized medicine approaches.
Methods: A case-control study was conducted with 210 PTC patients and 210 controls. Genotype frequencies were analyzed using Chi-Square tests, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Associations with clinical characteristics (T Status, N Status, Stage) were assessed in PTC patients.
Results: The MMP2 rs7201 CC genotype was significantly associated with increased PTC risk (OR = 3.524, 95% CI = 1.809–6.867, p = 0.001) and advanced T Status (T3: 48.6%, p = 0.029), but not with N Status (p = 0.509) or Stage (p = 0.461). The C allele was more frequent in cases (44%) than controls (32%) (OR = 1.590, p = 0.001). Conversely, MMP9 rs17576 showed no association with PTC risk (GG: OR = 0.727, p = 0.277) or clinical characteristics (p > 0.05). Both polymorphisms were in Hardy-Weinberg equilibrium in controls.
Conclusion: The MMP2 rs7201 CC genotype and C allele are associated with increased PTC risk and tumor progression, highlighting their potential as biomarkers for personalized risk stratification. These findings support genotype-based screening to identify high-risk PTC patients, enabling tailored surveillance and therapeutic strategies. Further studies are needed to validate these associations and explore their utility in precision medicine.

Abstract Background: The ASPN gene encodes a cartilage extracellular protein (Asporin) that is known to be involved in the pathological paths of osteoarthritis (OA). Many research efforts have explored the link between aspartic acid D-repeat polymorphism in the asporin (ASPN) gene and the risk of OA susceptibility, yet the findings are inconsistent. Our study involved a case-control analysis to examine the relationship between D allele polymorphism in asporin and primary hip osteoarthritis (HOA) among the Iranian population.
Methods: The asporin D repeat polymorphism was genotyped in primary HOA patients (N=70) and healthy controls (N=70). Each group consisted of 28 women and 42 men. Patients were classified into three subgroups based on the radiographic severity of osteoarthritis. Statistical analysis was performed on gender, severity, and primary HOA position.
Odds ratios (ORs) along with 95% confidence intervals (95% CIs) were utilized to assess the association between D-repeats in the ASPN gene and primary hip osteoarthritis.
Results: Three common D-repeat variants (D13, D14, and D15) of the ASPN gene were obtained. The most frequent allele in the patient group was observed at D13, while it was D15 among controls. In both cohorts, the least frequent allele was D14. Our findings indicate no statistically significant association between any D-repeats with primary HOA according to the sex of patients or the severity of the disease.
Conclusion: Our findings indicate that polymorphisms in the ASPN D-repeat are not linked to a higher risk of primary hip osteoarthritis (HOA) in the Iranian population.  However, future large studies are needed to validate these findings.

Abstract Aim: Oxidative stress is one of the main factors has been implicated in pathophysiology of cataracts. Superoxide dismutase (SOD) can prepare the first line of defense versus detrimental reactive oxygen species (ROS) and Sirtuin (SIRT) confers protection against oxidative stress and retinal degeneration. Correlation of SOD1-50bp ins/del and SIRT1-rs7895833 polymorphisms with risk of cataracts is not studied currently. Therefore, we aimed to explore possible relationship between SOD1 (50bp ins/del) and SIRT1 (rs7895833) polymorphisms with the risk of cataracts in Iranian population. 
Methods: Our study design consisted of 200 patients with age-related cataracts and 200 healthy individuals as a control group. After DNA extraction, the identification of polymorphisms was conducted using PCR-based methods and data analysis was done by SPSS software. 
Results: A significant difference in SOD1 DD genotype distribution was observed between studied groups (OR: 3.42, P:0.037), the D allele was more frequent in patients in comparison with controls (OR: 1.68, P:0.009). Also, in the dominant genetic model for the D allele (comparison between ID+DD vs. II), ID+DD genotypes increased the risk of cataracts (OR: 1.62, P: 034). The association between SIRT1-rs7895833 polymorphism and cataract was significant in the AG genotype (OR: 2.37, P<0.001) and G allele (OR: 1.97, P<0.001). The SIRT1-1 polymorphism increased the risk of cataracts in the dominant tested inheritance model (OR: 2.34, P<0.001). In the combined analysis of two polymorphisms, there is an additive effect of the high-risk putative alleles about the risk of cataracts. Risk estimation according to the number of high-risk alleles showed that χ2 for linear trend for 0, 1, 2, 3 and 4 putative high-risk alleles is equal to 20.10 (P<0.001). 
Conclusion: The results showed that for the first time, SIRT1 rs7895833 and SOD1-50bp ins/del gene variations had additive effects on the risk of cataracts.

Abstract Background: Lung cancer is the first cause of cancer deaths in the world. Pemetrexed is an antifolate drug used as a first or second-line in the treatment of advanced non-small cell lung cancer (NSCLC) patients. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in a folic acid metabolic pathway and a central role in clinical response to pemetrexed. The aim of this study was to investigate the association between rs1801133 polymorphism and the overall survival of metastatic NSCLC patients.  
Methods: Thirty-four patients with metastatic lung cancer were treated with pemetrexed-based regimen at Rasoul Akram Hospital, Tehran, Iran. Genomic DNA was extracted from the peripheral blood of patients before initiation of treatment. Genotyping of rs1801133 polymorphism was performed at the National Institute of Genetic Engineering by PCR-RFLP methods. Statistical analysis performed with SPSS software, version 21.0.
 Results: Thirty-four patients were enrolled in this study. 21 patients (62%) were male and 13 (38%) were female. The mean age of the patients was 58.90 years. rs1801133 polymorphism were not significantly associated with survival in patients treated with pemetrexed-based chemotherapy.
 Conclusion: Previous studies have demonstrated that MTHFR polymorphism may predict survival among pemetrexed-based regimen treated advanced non-squamous NSCLC patients. However, in this study, the examined polymorphisms were not associated with patients' survival.

Abstract Warning of the World Health Organization (WHO) indicates that novel coronavirus (COVID-19) is pandemic and causes global concern. COVID-19 has acute respiratory symptoms which leads to die in many cases through the world. We have found seven variants in 300 patients based on Next Generation Sequencing (NGS) which are related to infectious disease. According to the databases, we confirmed that rs2660 and rs1800450 have association with COVID-19 in the Iranian population.

Abstract PAI-1 has become recognized as a central molecule linking pathogenesis and progression of thrombotic vascular events, including stroke. Clinical and experimental studies show that PAI-1 deficiencies cause accelerated fibrinolysis and bleeding, whereas elevated PAI-1 plasma levels are associated with vascular thrombosis. Raised PAI1 plasma levels are related to a 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter of the PAI1 gene. The 4G allele is associated with higher plasma PAI1 transcription and activity. In the current study, the association of higher PAI-1 plasma levels and the prevalence of the 4G/5G polymorphism in the PAI-1 gene promoter region in young patients with stroke were explored. Significantly, higher PAI-1 levels were observed in patients when compared to controls (p =002). The 4G/5G polymorphisms were significantly associated with increased PAI-1 levels, with the variant homozygous 4G/4G corresponding to mean values in patients versus controls.

Abstract Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder. The etiology of MS is not clear but genetic and epigenetic factors are involved in MS development. Studies have shown that IL7R gene polymorphisms is capable of changing MS susceptibility. We investigated the association of MS with rs11567658, rs11567686 promoter polymorphisms of IL7R gene in western provinces of Iran. In the present study, 187 MS patients and 190 healthy control were evaluated. Polymorphic regions of IL7R promoter were amplified by appropriated primers and polymorphisms were then evaluated by RFLP method followed by validation via Sanger sequencing. Results shown rs11567685 and rs11567686 are significantly associationed with MS (P = 0.017 P = 0.046), significant association of these polymorphism with age was also found (P = 0.002). This study showed that IL7 receptor gene polymorphism has a key role in MS development and may be important opportunity for development of therapeutic and diagnostic strategies in context of personalized medicine.