polymorphism

The cytochrome P450 (P450s or CYPs) enzyme family, particularly CYP2D6, significantly influences drug metabolism, handling approximately 20-25% of prescribed medications. Understanding genetic polymorphisms is crucial for personalized medicine and optimizing drug therapy in specific geographic and racial contexts. Given the complex nature of studying CYP2D6 genotypes, this study aimed to assess the prevalence of rare CYP2D6 star alleles, including rs267608319 (CYP2D6*31), rs1931013246 (CYP2D6*55), rs569439709 (CYP2D6*113), and rs747089665 (CYP2D6*135), within the Iranian population.  Blood samples were obtained from 389 individuals across several ethnic groups in Tehran, Iran, from May to December 2022. PCR was used to amplify the region containing the desired variant. Genotyping was performed using the Sanger sequencing method. Our analysis revealed a high frequency of normal alleles for all four studied variants, indicating the absence of the risk allele in the Iranian population. These findings suggest that the studied alleles have no apparent effect on various ethnic groups in Iran. The Iranian population has a typical genetic makeup for CYP2D6 variations, impacting medication prescribing. Understanding genetic differences is crucial for personalized drug therapies. Further research into Iranian genetic variations is essential for advancing personalized medicine.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and the leading cause of childhood death in contrast to the 90% cure rate. ALL includes different subtypes described by interrupt collections of somatic chromosomal alterations and sequence mutations that disrupt normal body functions such as lymphoid maturation, cell-cycle regulation, and tumor suppression. Having a significant role in several cancers, the high mobility group box-1 (HMGB1) gene is considered an important gene in the development of tumors.

Herein, the genetic role of HMGB1 was studied in the 49 Iranian patients with newly diagnosed ALL using Sanger sequencing of HMGB1 coding regions (exons 2 to 5).

The results showed that none of the subjects in the study had any promising variants in the coding sequences of the HMGB1.

These findings suggest that HMGB1 is not directly associated with ALL incidence and behavior. Further investigations using a large group of patients with different races and ethnicities are required to analyze the possible role of HMGB1 gene polymorphisms in ALL patients.

Undernutrition disorder is a prevalent comorbidity (up to 25%) in type 2 diabetes (T2D) patients which significantly compromises their health. We aimed to assess the association between single nucleotide polymorphysms (SNPs) adiponectin (ADIPOQ) +276 (G/T) and resistin (RETN) -420 (C/G) with the risk of developing T2D and undernutrition in patients with T2D.

The research was conducted as prospective case-control study among 106 patients with T2D and 106 healthy control individuals in the territory of the Bosnia and Herzegovina from Sep 1st 2022 to May 1st 2023. For assessing the nutritional status, the mini nutritional assessment (MNA) was used. DNA analysis was carried out by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. The data were analyzed using chi-square test, t-test for independent samples and binary multivariate logistic regression.

The research included 212 subjects of which 124 (58.5%) were male. The mean age of the subjects was 68.48±4,67 yr. Almost 20% of subjects were undernourished, significantly more T2D patients when compared to controls (33% vs. 6.6%; P<0.001). ADIPOQ +276 GT genotype was identified as significant predictor of T2D (OR: 3.454; 95% CI: 1.400-8.521; P=0.007) and undernutrition disorder (OR: 3.453; 95% CI: 1.331-8.961; P=0.011) in T2D population, while the presence of RETN -420 CG genotype had protective effect against occurrence of T2D (OR: 0.353; 95% CI: 0.144-0.867; P=0.023). However, RETN genotypes were not associated with undernutrition disorder.

ADIPOQ +276 gene polymorphism represent a significant predictor for development of T2D and undernutrition disorder in T2D population, while RETN -420 gene polymorphism was identified as a significant factor associated with a reduced risk for T2D, but was not associated with undernutrition.

Genetic polymorphisms are considered potential causes of recurrent spontaneous abortions (RSA). This study aimed to determine the frequencies and association of rs1632944 and rs1632947 polymorphisms of the HLA-G gene promoter region with the RSA in women from northwest Iran.
This case-control study was conducted on 180 women referred to Madar Infertility Center and Al-Zahra Hospital in Tabriz. Ninety patients with a history of at least two RSA as the patient group and 90 women with at least one child and no history of abortion as the control group were included in the study. 5 ml peripheral blood was obtained from each person; genomic DNA was extracted, amplified by PCR, and genotyped with sequencing and ARMS methods. Data were analyzed using SPSS, Chi-square, and Fisher's exact tests.
For rs1632944 polymorphism, frequencies of the AA, AG, and GG genotypes were 34.44%, 45.55%, and 20% for the control group and 48.88%, 46.66%, and 4.44% for the patient group, respectively. We found that the minor allele G is recessive against major allele A and might protect women against RSA. For rs1632947 polymorphism, frequencies of the GG, AG, and AA genotypes were 52.22%, 35.55%, and 12.23% for the patient group and 64.44%, 32.22%, and 3.33% for the control group, respectively. We found that the minor allele A is recessive against the major allele G and is associated with the RSA.
The results showed that the rs1632944 and rs1632947 polymorphisms of the HLAG-G gene promoter, might be related to RSA in women from Northwest Iran.

The severity of coronavirus disease 2019 (COVID-19) varies significantly among individuals, which indicates the impact of individual differences on disease. Emerging evidence suggests that genetic factors play a crucial role in determining the severity of the disease. For instance, variants in the interferon-gamma (IFN-γ) gene, such as the +874 T/A single nucleotide polymorphism (SNP), have been linked to altered immune responses and may influence the severity of COVID-19. We aim to determine the influence of the IFN‐γ +874T/A SNP on the clinical outcomes of COVID-19 patients. We investigated the SNP at position +874 in the promoter region of the IFN-γ gene in 416 individuals (206 critically ill COVID-19 patients and 210 healthy controls) in northwestern of Iran. Genomic DNA was extracted from the blood leukocytes of the patients, and the SNP was analyzed using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. The AA genotype was significantly more frequent in critically ill COVID-19 patients than in healthy controls. Conversely, the AT and TT genotypes were more common in healthy controls. Furthermore, the A allele was more frequent in critically ill patients than in healthy controls, while the T allele was more frequent in healthy controls compared to critically ill patients. Our study identified the IFN-γ +874T/A SNP as a significant genetic factor influencing COVID-19 severity. This finding underscores the critical role of genetic factors in disease severity and highlights the importance of personalized medicine in managing COVID-19.

Hirschsprung disease (HSCR) is a congenital life-threatening intestinal disorder characterized by the absence of nerves in the myenteric and submucosal plexuses in the distal bowel. There are several studies on the association of rs2435357 polymorphism in the proto-oncogene RET gene and HSCR susceptibility. However, some of the results remain controversial. Therefore, we conducted this updated meta-analysis to estimate the association of this polymorphism and HSCR risk.

We searched PubMed, Scopus, Web of Science and Google Scholar according to PRISMA guidelines to assess the association of RET rs2435357 with HSCR up to Jan 2024. We included case-control/cohort studies to perform meta-analysis conducted using genotype models. Odd ratios (ORs) with 95%CI were utilized to determine the susceptibility to HSCR. Q-test and I2 were used to evaluate heterogeneity, and Egger’s/ Begg’s tests were used to assess publication bias.

Overall, 89 eligible studies meeting the inclusion criteria were retrieved with 2690 cases and 5408 controls from online databases. Finally, 17 studies were used for meta-analysis. RET rs2435357 showed a statistically significant association with HSCR under allelic model (OR = 4.50, 95%CI: 3.78-5.36, P<0.05), additive model (OR=2.02, 95%CI: 1.54-2.63, P<0.05), recessive model (OR=4.39, 95%CI: 3.33-5.78, P<0.05) and dominant model (OR=8.66, 95%CI: 6.96-10.76, P<0.05).

The polymorphism rs2435357 in RET gene provides substantial susceptibility in all inheritance models and to HSCR. However, more research is needed to clarify its specific role in prognosis and the interaction with other genetic and environmental factors affecting HSCR.

Pre-eclampsia (PE) is a severe pregnancy condition with genetic and environmental factors affecting the placental function and vascular changes. Genetic variants in the apelinergic system may influence preeclampsia risk and birth outcomes. Therefore, this study aimed to compare apelin (APLN) rs56204867 and apelin receptor (APLNR) rs11544374 gene polymorphisms and to investigate their association with mothers’ body mass index and infant's birth weight among women with preeclampsia and control group in southeast Iran.

A total of 123 PE patients and 125 age- and gender-matched control subjects were enrolled in the study. The PCR–RFLP method was employed to genotype the APLN rs56204867 and APLNR rs11544374 gene polymorphisms.

 There was no significant association between the genotypes of the rs11544374 variant and the PE risk. The incidence of the AG genotype of the rs54204867 variant in the control group was considerably greater than in the PE group. Also, a significant relationship was found between the body mass profile of patients with PE and the APLN rs54204867 gene polymorphism.

It was observed that the APLN rs54204867 gene polymorphism could affect the PE risk. No significant difference was found between the PE group and the control group in terms of the genotypes of the APLNR rs 11544374 variant. It was not statistically significant between mothers' BMI and rs11544374 of the APLNR gene, whereas an obvious link was observed between Mothers' BMI and rs54204867 of the APLN gene.

Genetic predispositions have been identified as important factors in male infertility. Among the many genes related to male reproductive function, interleukin 6 (IL-6) has emerged as a key player. Despite the growing recognition of genetic factors in male infertility, the specific association between the IL-6-174 G/C genetic polymorphism and male infertility remains an area that needs further investigation.

This investigation explores the correlation between the IL-6-174 G/C transversion and male infertility.

In a case-control study, a total of 314 men who referred to the Kashan Infertility Centre, Shahid Beheshti hospital, Kashan, Iran, were enrolled for IL-6-174 G/C polymorphism analysis. The study comprised 163 infertile participants as the case group and 151 fertile men as the control group. Following the screening, 2 ml of whole blood was collected from each participant. Cases were categorized into 3 subgroups based on World Health Organization criteria: (i) nonobstructive azoospermia (n = 42), (ii) oligozoospermia (n = 61), and (iii) asthenozoospermia (n = 60). After DNA extraction, genotypes of the samples at the -174 G/C (rs1800795) locus were determined using the polymerase chain reaction-restriction fragment length polymorphism method.

Our genetic investigation demonstrated a significant association between the GC genotype and male infertility. Furthermore, a correlation was observed between the heterozygous GC genotype and reduced risk of oligozoospermia and asthenospermia. Additionally, the C allele was correlated with a decreased risk of infertility and specific subgroups such as oligozoospermia and asthenospermia.

Our findings suggest that the IL-6-174 G/C transversion could potentially serve as a protective genetic factor against male infertility.

Clinical studies have shown that variations in the ACE2 gene can influence susceptibility to and the severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. Although the evidence is not conclusive, recent studies have suggested a potential link between the ACE2 rs2285666 polymorphism and COVID-19.

This multicentric clinical study, conducted in Lorestan and Golestan provinces, aimed to examine the association between the ACE2 rs2285666 polymorphism and COVID-19 in Iranians of various ethnicities, including Fars, Lur, Turkmen, and Balooch.

A total of 372 participants were evaluated, with 201 testing positive for SARS-CoV-2 and 171 negative. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique, using the AluI enzyme, was employed to identify the polymorphism. Demographic and clinical data were analyzed using IBM SPSS. Hazards were assessed through odds ratio analysis, while Hardy-Weinberg equilibrium (HWE) and genotype variations were evaluated using SNPSTATS.

PCR-RFLP analysis indicated that the AA genotype may increase susceptibility to COVID-19. Among female COVID-19-positive patients, 56%, 29%, and 15% exhibited GG, GA, and AA genotypes, respectively, compared to 61%, 35%, and 4% in the control group. In male individuals, the frequencies of G and A genotypes were 89% and 11% in the healthy group, while they were 25% and 75%, respectively, in the patient group. Polymorphism frequencies were not in HWE in both the positive and negative groups (P < 0.05). Logistic regression analysis showed that the AA genotype differed in co-dominant and recessive inheritance models, with odds ratios (OR) of OR = 4.06 (1.10 - 15.00) and OR = 4.21 (1.16 - 15.24). The ACE2 rs2285666 AA or A genotype was strongly associated with an increased risk of COVID-19 in this study.

A significant difference in the distribution of the AA and A genotypes was observed in COVID-19 patients. Further studies involving larger and more diverse populations are necessary to explore the impact of this polymorphism on the susceptibility to and severity of COVID-19.

In this study, we investigated the relationship between polymorphisms in the adiponectin gene and biochemical parameters—specifically adiponectin levels, insulin resistance, and the presence of non-alcoholic fatty liver disease (NAFLD)—in an Iranian population.

We conducted a case–control study comprising 80 individuals with NAFLD and 80 healthy controls. Genotyping of the ADIPOQ gene polymorphisms rs17300539, rs266729, and rs1501299 was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, while serum adiponectin and insulin levels were quantified via enzyme linked immunosorbent assay (ELISA).

Our findings demonstrated that patients exhibited significantly higher serum triglyceride levels, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diastolic blood pressure compared to healthy individuals. In contrast, adiponectin and high density lipoprotein cholesterol (HDL-C) levels were significantly lower in patients, and body mass index (BMI) was significantly elevated (P < 0.05). None of the analyzed single nucleotide polymorphisms (SNPs) were associated with insulin resistance. However, there was a significant difference in both genotype and allele frequencies of the rs1501299 variant between the patient and control groups. Additionally, within the case group for rs17300539, GA carriers had a higher BMI than GG carriers. Moreover, significant associations were observed between the rs17300539 and rs266729 polymorphisms and AST levels (P < 0.05).

Our results suggest that the G allele of rs17300539 in the adiponectin gene may play a protective role by reducing the complications associated with NAFLD, while the rs1501299 polymorphism appears to be associated with an increased risk of NAFLD.

 Polymorphisms within the excision repair cross-complementation group 1 (ERCC1), an essential component of DNA repair mechanisms, have been associated with various malignancies. This study aimed to evaluate the association of the single-nucleotide polymorphisms (SNPs) rs3212986 and rs11615 within the ERCC1 gene in non-small cell lung cancer (NSCLC) patients.

Study Design: 

A case-control study.

 Genomic DNA was extracted from the peripheral blood samples of 83 NSCLC patients and 119 healthy individuals. The genetic diversity of SNPs rs3212986 and rs11615 was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The RFLP results were confirmed through sequencing.

 The TT genotype of the rs11615 SNP was associated with a higher risk of NSCLC development (odds ratio: 3.900, 95% confidence interval: 0.603, 22.866, P=0.050). Furthermore, the AA genotype of rs3212986 was related to a higher risk of NSCLC development (OR: 2.531, 95% CI: 1.017, 6.300, P=0.046). A significant association was observed between smoking and lung cancer (OR: 3.072, 95% CI: 1.715, 5.503, P<0.001). Moreover, among non-smokers, there was an association between lung cancer risk and the AA (OR: 6.825, 95% CI: 1.722, 27.044, P=0.006) and AC (OR: 2.503, 95% CI: 0.977, 6.412, P=0.056) genotypes of rs3212986. However, no correlation was found between the genotypes of these SNPs and patients’ sensitivity to cisplatin and carboplatin (P ˃ 0.05).

 The rs11615-related TT genotype and the rs3212986-related AA genotype may be associated with a higher risk of lung cancer development.

Hepatitis virus infections are among the serious emerging health issues. They are the primary causes of cirrhosis and hepatocellular carcinoma. Growing evidence shows a link between certain genomic variations and inflammation including viral infection such as HBV and HCV. Therefore, this study aimed to comprehensively review studies that analyze the effect of host genomic variations on the risk of contracting viral hepatitis in Iranian population.

The study was conducted according to the PRISMA Statement. All Persian and English case-control articles published until the beginning of June 2023 were included in the study. Two authors reviewed the articles independently. The third author reviewed the final results. Pathway analysis and protein interactions were also performed using GO and STRING databases.

Seventy relevant studies were retrieved. Fifty-three studies examined the association of SNPs with the risk of HBV infection. In terms of genetic variations, 25 genes and 44 SNPs were identified. Tumor necrosis factor alpha, Interleukin 28B, and Interleukin 10 were the most prevalent considered genes. The most common polymorphisms were in the interleukin family. Moreover, the top five identified molecular functions were cytokine activity, cytokine receptor binding, molecular function regulator, protein binding, and signaling receptor binding.

The polymorphisms of genes involved in the production of immune factors, cytokines, interleukins, and their receptors are associated with the risk of HBV and HCV infections in the Iranian population. Moreover, the extracellular and intracellular signaling pathways and the regulating molecules of these processes can be considered as important factors in liability for these viral infections.

Oral Squamous Cell Carcinoma (OSCC) is a pressing global health challenge. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators. Among these, the lncRNA ANRIL (antisense non-coding RNA in the INK4 locus) has a role in cancer progression. The aim of this study was to look into possible links between a certain genetic variant of lncRNA ANRIL, rs10757278 A/G, and OSCC risk and tumor features in the Iranian population.

We conducted a case-control study, enrolling 101 OSCC patients and 115 healthy controls. We took out the genomic DNA and used the tetra-primer ARMS-PCR (tetra-primer amplification refractory mutation system-polymerase chain reaction) method to find the rs10757278 genotype. We evaluated the associations between genotypes and both OSCC susceptibility and various tumor characteristics.

Although we did not observe significant differences in allele and genotype frequencies between cases and controls, we revealed compelling associations between genotypes and tumor characteristics. Genotypes AG and GG were linked to smaller tumor sizes, while genotypes with at least one wild-type allele (A) were linked to well differentiated OSCC. Specific genotypes exhibited significant associations with tumor sites, with the tongue demonstrating the strongest correlation.

The rs10757278 A/G variant did not show a direct link with OSCC risk, but its complex effect on tumor behavior suggests that it may play a bigger role in the development of OSCC. These findings open avenues for future investigations to uncover hidden genetic interactions, and potentially inform more targeted therapeutic strategies.

Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear.

This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles.

Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant.

Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage.

The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most prevalent congenital birth anomaly. The EPHA3 gene is suggested to play a pivotal role in the development of oral clefts.

This study aimed to evaluate the influence of EPHA3 gene polymorphisms on the risk of NSCL/P within an Iranian cohort.

We performed genotyping of the EPHA3 gene polymorphisms rs7650466, rs1398197, rs17801309, rs1054750, and rs7632427 in 150 NSCL/P patients and 152 healthy controls using PCR-RFLP, T-ARMS-PCR, and ARMS-PCR methods.

The results indicated that the rs1398197 variation significantly reduced the risk of NSCL/P in a heterozygous codominant model (OR = 0.58, 95% CI = 0.36 - 0.94, P = 0.027, G/A vs. G/G), a dominant model (OR = 0.56, 95% CI = 0.35 - 0.89, P = 0.014, G/A + A/A vs. G/G), and at the allele level (OR = 0.62, 95% CI = 0.43 - 0.91, P = 0.014, A vs. G). The rs1054750 polymorphism showed a decreased risk of NSCL/P in codominant (OR = 0.62, 95% CI = 0.39 - 0.99, P = 0.047, T/C vs. T/T) and dominant models (OR = 0.62, 95% CI = 0.39 - 0.98, P = 0.042, T/C + C/C vs. T/T). The rs17801309 polymorphism was not associated with any risk or protection from NSCL/P. rs7650466 and rs7632427 were not polymorphic in the study sample.

Our findings suggest that variants of the EPHA3 gene may be linked with a reduced risk of NSCL/P.