polymorphisms

Colorectal cancer (CRC) is one of the leading causes of death worldwide and is increasingly recognized as a heterogeneous disease at the molecular level. The autophagy-related 5 ( ATG5 ) and light chain 3 ( LC3B ) genes are involved in the autophagy pathway and play crucial roles in physiological processes, including adaptation to starvation, prevention of neurodegeneration, expression of intracellular antigens, and tumor suppression.

This study aimed to elucidate the epigenetic alterations in the ATG5 and LC3B genes and analyze the polymorphism of ATG16L1 in CRC.

This case-control study included 320 blood samples divided into case and control groups, comprising 160 CRC samples and 160 healthy samples. Restriction fragment length polymorphism (RFLP) was used to genotype the ATG16L1 (Thr300Ala) polymorphism, while methylation-specific PCR (MS-PCR) was employed to assess promoter methylation of the ATG5 and LC3B genes. Logistic regression was used to compare methylation patterns and genotypes between case and control groups. Additionally, the chi-square test was applied to compare demographic variables between groups.

The data analysis revealed a significant difference in the methylation patterns of ATG5 and LC3B between the case and control groups. The promoter methylation status of the LC3B gene candidate region exhibited a lower methylation pattern in the case group (37.3%) compared to the control group (69.4%) (P < 0.001). Conversely, the ATG5 gene promoter showed higher methylation levels in the case group (80.8%) than in the control group (43.8%) (P < 0.001).

This study analyzed methylation changes in the ATG5 and LC3B genes in CRC patients. The findings suggest that alterations in the promoter methylation patterns of ATG5 and LC3B play significant roles in the pathogenesis of CRC. Additionally, the mutant genotype of ATG16L1 rs2241880 may increase susceptibility to CRC.

To assess the possible association between MIR200B variations and sight-threatening diabetic retinopathy (STDR).

A total number of 141 diabetes mellitus patients were enrolled in the study and divided into two groups including 76 patients diagnosed with STDR assigned to the case group, and 65 subjects without STDR considered in the control group. Peripheral blood specimens were used to extract the DNA content, and the primary MIR200B encoding sequence was amplified using a polymerase chain reaction. Then, the amplified DNA was sequenced by the Sanger method. The sequences were compared to the MIR200B reference sequence to find sequence variations. RNAfold, miRVaS, and Mfold bioinformatics web servers were employed to predict the potential effects of the identified variations on RNA structure.

Two MIR200B gene variants were identified. Although both variations were found more frequent in cases than controls, statistical analysis of allelic and genotypic features did not reach statistical significance.

In silico analysis showed mild changes in MIR200B secondary structure and increased free energy in the presence of one of the identified variants (g.1167183G>A; rs72563729). Increasing the sample size in future studies may help a more accurate interpretation of the allelic association of MIR200B variations with STDR.

Down syndrome (DS) is a complex genetic disease that is caused by having three copies of chromosome 21. A possible association between polymorphisms in maternal folate metabolism genes and DS has been evaluated.

It was aimed to first investigate the influence of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and plasma homocysteine (Hcy) on the maternal risk for DS in the southwest of Iran.

The MTHFR C677T and A1298C polymorphisms were genotyped using restriction fragment length polymorphism and Sanger sequencing, respectively. Allele and genotype frequencies and the dominant model of the MTHFR C677T and A1298C polymorphisms were evaluated in 80 mothers of children with DS and 80 control mothers. Eventually, the ELISA test was used to compare the concentration of plasma Hcy in both groups.

A significant association was observed in the 677T and 1298C alleles between the mothers of DS and control groups (P = 0.00077 and P = 0.01248, respectively). Further, the median concentrations of Hcy were significantly higher in mothers with DS babies compared to the control group (P < 0.05).

There was an association between MTHFR C677T, A1298C, and plasma Hcy concentrations as the maternal risk of mothers with DS children.

Polymorphisms in the vitamin D receptor (VDR) play an effective role in the susceptibility of pulmonary tuberculosis (TB). Given the importance of this polymorphism and its association with pulmonary TB, this study aimed to investigate the prevalence of VDR polymorphisms in people with pulmonary TB.  

The search process was performed from 2009 to 2023 according to PRISMA (Preferred reporting items for systematic reviews and meta-analyses). The strengthening of the reporting of observational studies in epidemiology (STROBE) checklist was used to qualify the articles. The data was entered into STATA version 14 software, then the fixed effects model and the random effects model, effect size (ES), and Q test (P < 0.10) were used for data analysis at a confidence interval level (CI) of 95%. Two-sided statistical tests were considered with α=0.05.  

In this research, 28 articles were analyzed. Polymorphisms showed a significant relationship with susceptibility to pulmonary TB (P = 0.000), and significant heterogeneity (P = 0.000) was seen between polymorphisms. FokI (95% CI: 0.39-0.46, P = 0.000, ES = 43%), ApaI (95% CI: 0.31-0.48, P = 0.000, ES = 39%) and BsmI  (95% CI: 0.24-0.50, P = 0.000, ES = 37%) showed the most frequent gene polymorphisms after TaqI (95% CI: 0.34-0.77, P = 0.000, ES = 56%).  

ApaI, BsmI, FokI, and TaqI polymorphisms were found in patients suffering from pulmonary TB. Polymorphisms related to the TaqI gene were the most frequent. Controlling and prescribing vitamin D may be needed in these patients.

Graves’ disease (GD) is an autoimmune disease that is associated with increased thyroid gland irritation and, consequently, hyperthyroidism. Autoimmune diseases are common in the general population and are influenced by genetic and environmental factors. PTPN22, which was reported as a susceptible locus for GD in several populations, acts as a negative regulator for activation of primary T-cells, and LYP polymorphism could potentially increase susceptibility to Graves' disease, which may play a role in other autoimmune conditions as well. In this study, we investigated the association of several PTPN22 single nucleotide polymorphisms (SNPs) with Graves patients.

After DNA extraction from peripheral blood cells, SNP Genotyping was performed through real-time PCR with allelic discrimination TaqMan genotyping assays (ABI Applied Biosystems, 7300 Real-Time PCR System, USA) based on manufacturer protocols. The frequencies of alleles and genotypes of PTPN22 SNPs (rs12760457, rs2476601, rs1310182, and rs1217414) were recorded.

In our study, the rs1310182 was significantly more frequent in patients with GD than in healthy individuals. While the C allele of rs1310182 was 1.78 times more frequent in GD patients (95%CI: 1.18-2.69, P=0.005), the T allele was more frequent in healthy subjects (OR=0.56, 95% CI: 0.37-0.84, P=0.005). In addition, the CC genotype of this SNP was 1.86 times more common in patients (P=0.05). No significant differences were observed between the other SNPs of this gene in case and control.

The results demonstrate that one SNP (rs1310182) of the PTPN22 gene is associated with susceptibility to GD in an Iranian population. Further studies, including functional analyses, are required.

Leptin is thought to play an important role in Crohn’s disease (CD) pathogenesis and progression. Independent studies have revealed a strong upregulation of leptin expression in the mesenteric fat of CD patients.

This study assessed the relationship between leptin gene polymorphisms and CD susceptibility in a Chinese pediatric population.

A total of 86 patients withCDand 142 healthy controls were recruited for this case-control study. The genotypes of 4 singlenucleotide polymorphisms (SNPs; rs2071045, rs41457646, rs11761556, and rs2167270) in the leptin gene were determined by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing.

We found that leptin rs2167270 had a significantly different distribution of alleles and genotypes between CD patients and healthy controls (G is a risk allele: 83.7% of cases vs 72.5% of controls; odds ratio [OR] 1.947; 95% CI, 1.203-3.151; P = 0.006; GG is a risk genotype: 72.1% of cases vs 53.5% of controls; P = 0.021). Patients with the CC genotype (rs2071045) had a significantly increased risk of early onset of CD (58.3% in A1a vs 31.1% in A1b; P = 0.003). Similarly, patients carrying the G allele (100% in A1a vs 84.1% in A1b; P = 0.015) and GG genotype (100% in A1a vs 71.0% in A1b; P = 0.048) of rs41457646, A allele (93.3% in A1a vs 71.8% in A1b; P = 0.013) and AA genotype (93.3% in A1a vs 47.9% in A1b; P = 0.003) in rs11761556 had a higher risk of early onset of CD. However, there was no significant difference in any of these 4 SNPs between patients with and without perianal lesions, as well as in low and normal body mass index (BMI) patients.

The leptin rs2167270 polymorphism is associated with the susceptibility toCDin a Chinese pediatric population. Leptin rs2071045, rs41457646, and rs11761556 might lead to the early onset of pediatric CD.

Context: 

The relationship between polymorphisms in the location of the cytokine tumor necrosis factor (TNF-α) and lung cancer has been investigated in many studies. Accordingly, the present meta-analysis study focused on the relationship between the TNF-α-238 gene polymorphisms and lung cancer.

 Articles were collected from Google Scholar, Scopus, and PubMed electronic databases until 2022. The articles were searched based on the keywords “Lung cancer,” “238 Gene”, and “tumor necrosis factor.” The articles were selected based on the PRISMA flow diagram.

 There was no bias in this study research. Two except for two studies were significantly different, while no significant difference was found in the other studies. However, the results of the final Overall OR with a value of (0.66; 1.88) OR = 1.11 indicate that the additive model in the TNF-α-238 (rs361525) SNP increases the risk of lung cancer in the random model (P < 0.01).

 The results of this meta-analysis study show the relationship between TNF-a-238 and lung cancer. The TNF-a-238 polymorphism increases the risk allele, and TNF-a-238 with an OR = 1.11 has an additive effect on lung cancer development and increases the risk of lung cancer.

This study aimed to assess MOB1A and B gene polymorphisms in patients with oral lichen planus (OLP. Several of premalignant lesions such as, leukoplakia, erythroplakia, oral lichen planus (OLP), and submucosal fibrosis can undergo malignant transformation and lead to oral cancer and non-invasive screening of patients to find those susceptible to SCC before progression to cancer would be highly beneficial.

This case-control study was conducted on 35 OLP patients and 35 healthy controls presenting to the Oral Medicine Department of Zahedan Dental School 2015 -2017. Unstimulated saliva samples were collected from both groups, and MOB1A and B gene polymorphisms were assessed by polymerase chain reaction (PCR). The two groups were compared by the Chi-square test (alpha=0.05).

Two groups had no significant difference in the frequency of T and G alleles for MOB1A gene polymorphisms. (P>0.05) and either two groups had no significant difference in the frequency of A and C alleles for MOB1B gene polymorphism's (P>0.05).

The present results showed no significant difference between the case and control groups regarding MOB1A and B gene polymorphisms; thus, MOB1A and B gene polymorphisms do not appear to play a role in the pathogenesis of OLP.

The results of case-control studies on the association between vitamin D receptor gene (VDR) polymorphisms and polycystic ovary syndrome (PCOS) are inconclusive.

We aimed to more precisely evaluate the correlation between the ApaI, BsmI, FokI, and TaqI VDR gene polymorphisms and PCOS susceptibility.

PubMed, Scopus, Science Citation Index, and Google Scholar databases were searched to retrieve related reports released up to the end of 2020. To evaluate the association strength of the VDR gene polymorphisms with PCOS risk, pooled ratios (OR) with a 95% confidence interval were determined.

In total, 1,119 subjects (560 PCOS cases and 559 controls) from 7 studies were included which met the inclusion criteria. A statistically significant association between the TaqI polymorphism and PCOS susceptibility was found in the Eastern Mediterranean Regional Office population (T vs. t: OR = 0.715; TT vs. tt: OR = 0.435, p < 0.001; TT vs. Tt+tt: OR = 0.696, p = 0.01; tt vs. TT+Tt: OR = 1.791, p < 0.001). It was found that the ApaI variant was a risk factor in the dominant inheritance model (AA vs. Aa+aa: OR = 1.466, p = 0.01) and the FokI polymorphism was a protective factor in the recessive inheritance model (ff vs. FF+Ff: OR = 0.669, p = 0.04). The VDR BsmI polymorphism did not show association with PCOS susceptibility.

Our meta-analysis revealed that the VDR ApaI in the dominant model, VDR FokI in the recessive model, and VDR TaqI polymorphisms in all genetic models are associated with vulnerability to PCOS. However, further studies with a larger sample size are required.

FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases.

To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics.

Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed.

The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity.

FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.

Atherosclerosis is known as an inflammatory disease that can affect any vessel in the body. The occurrence of atherosclerosis in heart vessels is called coronary artery disease (CAD). CAD is one of the most significant causes of morbidity and mortality in developed countries. Different genetic and environmental factors can cause cardiovascular diseases, such as age, weight, sex, and low high-density lipoproteins (HDL) levels. Antioxidant and anti-atherogenic effects of HDL are related to proteins attached, such as Paraoxonase (PON). The Paraoxonase gene family has three members, PON-I, PON-II, and PON-III, located next to each other, on the long arm of chromosome 7, in humans. It seems polymorphisms and genetic variation resulting in several different phenotypes can affect the PON function. Due to its role in the human antioxidant system, changes in paraoxonase activity can increase or even reduce the risk of CAD. In this investigation, we reviewed different studies that showed, in some populations, specific polymorphisms with an effect on enzymatic activity ultimately increase or decrease the risk of disease in individuals. In contrast, no association has been found between disease and polymorphism in some populations. Therefore, further studies and meta-analyses in this field seem to be useful.

Breast cancer is a phenotypically complex and diverse genetic disease caused by changes in the structure and expression of specific genes. Immune system factors are also involved in the etiology of this neoplasm. This study aimed to evaluate the effect of genetic changes (rs2243250 & rs2227284) on the interleukin 4 gene and body mass index on breast cancer risk in Iranian women.

From women referring to Shohada-Tajrish Hospital, 100 women with breast cancer and 100 healthy women were selected. After blood sampling and DNA extraction, the women’s genotypes were determined using the RFLP-PCR technique. The results were evaluated by SPSS software version 21 and chi-square and logistic regression tests.

Analysis of the results with different genetic models showed the effect of rs2243250 on breast cancer (p<0.05), but rs2227284 was not associated with breast cancer (p>0.05). People with the CC / TT genotype (polymorphism) were more likely to get breast cancer. Also, the increase in body mass index was significantly associated with both polymorphisms studied. Also, carriers of the TT genotype of rs2243250 polymorphism were more likely to develop breast cancer with aging.

Genetic alterations in the IL-4 gene and obesity probably contribute to breast cancer, and carriers of both genetic modifications (CC / TT) are more likely to develop breast cancer.

Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. 182 children with INS and 100 healthy controls were enrolled in this study. Blood genomic DNAs were used to analyze20 single nucleotide polymorphisms (SNPs) in 8 cytokine genes includingIL-21, IL-18, IL-6, IFN-γ, IL-4, IL-10, IL-17F, IL-17A d by multi-PCR with next-generation sequencing. Among 182 children with INS, 89 (48.6%) were steroid-sensitive (SS), 73 (39.9%) were steroid-dependent (SD) and 21 (11.5%) were steroid-resistant (SR). In 20 SNPs, IL-4-rs2243283 exhibited a significantly different genotype distribution between INS and the healthy controls (CC is a risk genotype: 66.5% of INS VS 51% of the control; OR=1.91, p=0.012). Patients carrying AG genotype (rs2275913, IL-17A) had a significantly higher risk of steroid-dependent response (69.1% of SD VS 46.4% of SS; OR=2.58, p=0.014). Similarly, patients carrying A allele of IL-10-rs1800872 (39.0% of SD VS 26.7% of SS; OR=1.76, p=0.018) and C allele of IL-10-rs1800896 (12.3% of SD VS 3.9% of SS; OR=3.44, p=0.004) had a higher risk of steroid-dependent response. However, none of these 20 SNPs showed a significant difference between SS group and SR group. Among the 20 cytokine gene SNPs, IL-4-rs2243283 might increase the susceptibility to INS in Chinese children; rs2275913 of IL-17A, rs1180972, and rs1800896 of IL-10 show association with the steroid -response in Chinese INS children.

The aim of this case–control study was to determine the impact of environmental factors on the predisposition to develop keratoconus in a sample of Western Algerian population. Subsequently, we were interested in the implication of two single nucleotide polymorphisms (SNPs) IL4 rs2070874 and FOXP3 rs3761548, previously described as contributing to the occurrence of allergy, in the development of keratoconus.

The study included 70 unrelated KC cases and 70 controls originating from Western Algeria. DNA genotyping was done using predesigned probe-based allelic discrimination TaqMan® assays. Allele and genotype frequencies were compared between the cases and controls by Chi-square test and odds ratios with 95% confidence intervals.

A significant association between risk factors such as family history, atopy, eye rubbing, and the development of keratoconus was found in our sample. Smoking would provide a protective effect against the pathology. No statistically significant differences were found in the allele and genotype frequencies between cases and controls neither for IL4 rs2070874 nor for FOXP3 rs3761548.

Our study provides, for the first time, a clear demonstration of the absence of association of the allergy-associated IL4 and FOXP3 polymorphisms with KC in a sample from Western Algerian population.

polycystic ovary syndrome (PCOS) is the most common cause of ovarian dysfunction associated with infertility, Oligomenorrhea or amenorrhea, hirsutism, acne, and obesity. A large body of evidence unraveled, three major groups of genes play critical roles in underlying PCOS molecular mechanism. The aim of this study is to investigate critical exonic variant of FSHR, CYP11, and INSR and determine the functionality of these mutations in Iranian patients with PCOS.

In this case-control study, 130 patients with PCOS who referred to the Vali-e-Asr Hospital with infertility were included. 3 ml peripheral blood was taken from the participants for DNA extraction. PCR was conducted for each gene and the PCR product was genotyped by sequencing.

The data showed that there were two polymorphisms in INSR genes which did not change the protein sequences; these alterations can also be considered as a single nucleotide polymorphism (SNP). Moreover, any exonic variant has not been detected in CYP11B1. Whereas, two missense mutation have been detected in FSHR gene including p.Ala307Thr and p. Asn680Ser. It has been shown that the polymorphisms of the FSHR gene affect the hormone response in the ovaries. Our data demonstrated that the FSHR mutations frequencies were higher in the patients with PCOS rather than control people (without any infertility complication) significantly.

Altogether, our data showed that the polymorphisms of FSHR were significantly associated with PCOS in Iranian infertile women. Further studies with larger sample sizes are needed to be performed in order to explore the strength of the association.

Estrogen, a crucial hormone during pregnancy, acts through two types of receptors. The estrogen receptor alpha and beta (ESR-α and ESR-β) are more abundant and exists in all human reproductive systems. Association of ESR-α and ESR-β genes polymorphisms has been reported in some reproductive problems such as spontaneous abortion, endometriosis-related infertility, and in vitro fertilization failure. In the present study, we investigated association between single nucleotide polymorphisms rs9340799 and rs2234693 (ESR-α) and rs1256049 and rs4986938 (ESR-β) with implantation failure in Iranian women.

In this case-control study, we collected 60 women with implantation failure as case group and 60 age and ethnically matched IVF-treated women with successful implantation as controls. Extraction of genomic DNA of both case and control members was performed using salting out method. The case and control groups genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR) method.

There were no significant differences in the frequencies of genotype and allele frequency in ESR-β gene rs4986938 polymorphism between patients and control groups (p>.005). In contrast, we observed a significant difference in the frequencies alleles and genotypes of rs9340799 and rs2234693 (ESR-α) and rs1256049 (ESR-β) polymorphisms between patients and control groups.

We demonstrated that rs9340799 and rs2234693 (ESR-α), and rs1256049 (ESR-β) polymorphisms may play important role in implantation failure in women in northwest of Iran. However, more studies on different geographic areas, races and ethnicities are required to determine exact role of ESR-α and ESR-β genes polymorphisms in implantation failure.

The decisive etiology of Oral squamous cell carcinoma (OSCC)  is still ambiguous, but we recognize the contribution of genetic aberration and environmental agent due to OSCC initiation. In the current study, we elucidate the potential impact of EGFR gene polymorphisms in the risk of OSCC in the southeast of Iran.

Forty-eight OSCC patients along with 100 normal volunteers were included. Three polymorphisms of EGFR gene (rs2227983, rs2293347 and rs2227984) were genotype by Tetra-ARMS PCR. Data analyzed with chi-square test and P-value < 0.05 was considered significant.

In rs2227983, the frequency of AG and GG genotypes were 62.5%, 37.5% in cases and 42%, 57% in the control group (P = 0.02, OR = 2.3) and also A allele frequency was 31.3% in case and 22% in the control (P= 0.08, OR= 0.62). AG + AA genotype frequency was 62.5% and 43% in case and control, respectively (P = 0.03, OR = 2.2). In rs2227984 and rs2293347 no statistical differences showed in the distribution of genotypes between the case and control group, also the majority of the OSCC has belonged to the grade I (43.8%).

The present investigation indicated that rs2227983 polymorphism may contribute to OSCC susceptibility in the southeast population of Iran. Although with the inconsistent interpretation mentioned due to the various geographical residency and different populations, more study of major population suggested being performed our finding validation.

The endothelial nitric oxide synthase (eNOS) gene encodes the eNOS enzyme in humans; it synthesizes nitric oxide (NO), which prevents or promotes colorectal cancer (CRC) progression. Polymorphisms of eNOS are correlated with the probability of cancer, but the findings are not consistent.

The present study aimed at investigating the correlation of eNOS rs1799983 polymorphism with CRC compared to the control group.

The eNOS rs1799983 polymorphism (G894T) was assessed in 100 healthy control subjects and 100 patients with CRC. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were utilized to analyze the eNOS polymorphism.

The risk of CRC in genotypes TT and GT of eNOS G894T polymorphism was significantly greater than genotype GG. The frequencies of genotypes TT and GT were 6% and 37% in the controls and 28% and 44% in the patients, respectively. The frequency of TT and GT genotypes showed a significant difference between patients with CRC (adjusted odds ratio (OR = 3.1, 95% confidence interval (95% CI) = 1.6 - 3.2; P = 0.001) and controls (adjusted OR = 1.8, 95% CI = 0.6 - 2.5; P = 0.005).

According to the results of the present study, allele T of eNOS G894T had a significant correlation with CRC even after adjusting for traditional risk factors.