Association Of Gene Polymorphisms Research Articles

Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children

To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Association of Polymorphism in Leptin Gene with Semen Quality Parameters in Egyptian Buffaloes Bulls

Association of Polymorphism in Leptin Gene with Semen Quality Parameters in Egyptian Buffaloes Bulls

IDF23-0338 Association of RAGE gene polymorphism with Type 2 diabetes mellitus and renal function in the Mexican population

IDF23-0338 Association of RAGE gene polymorphism with Type 2 diabetes mellitus and renal function in the Mexican population

Association of UGT1A Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients.

BK virus (BKV) infection is an opportunistic infectious complication and constitutes a risk factor for premature graft failure in kidney transplantation. Our research aimed to identify associations and assess the impact of single-nucleotide polymorphisms (SNPs) on metabolism-related genes in patients who have undergone kidney transplantation with BKV infection. <p> Material/Methods: The DNA samples of 200 eligible kidney transplant recipients from our center, meeting the inclusion criteria, have been collected and extracted. Next-generation sequencing was used to genotype SNPs on metabolism-associated genes (CYP3A4/5/7, UGT1A4/7/8/9, UGT2B7). A general linear model (GLM) was used to identify and eliminate confounding factors that may influence the outcome events. Multiple inheritance models and haplotype analyses were utilized to identify variation loci associated with infection caused by BKV and ascertain haplotypes, respectively. <p> Results: A total of 141 SNPs located on metabolism-related genes were identified. After Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) analysis, 21 tagger SNPs were selected for further association analysis. Based on GLM results, no confounding factor was significant in predicting the incidence of BK polyomavirus-associated infection. Then, multiple inheritance model analyses revealed that the risk of BKV infection was significantly associated with rs3732218 and rs4556969. Finally, we detect significant associations between haplotype T-A-C of block 2 (rs4556969, rs3732218, rs12468274) and infection caused by BKV (P = 0.0004). <p> Conclusions: We found that genetic variants in the UGT1A gene confer BKV infection susceptibility after kidney transplantation.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and β -Globin gene primers was performed. GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)]and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.

Association of OX40L gene polymorphism with multiple sclerosis in Iranians

IntroductionThe exact etiology of multiple sclerosis is unknown but recent studies indicated a link between tumor necrosis factor superfamily member 4 and the disease. Polymorphisms located in the regulatory region of the gene may affect its phenotype. Hence, we aimed to investigate the association of promoter polymorphisms of the gene with multiple sclerosis and also to estimate the frequency of haplotypes in the patients and healthy subjects. MethodsTwo hundred age- and sex-matched subjects including 100 patients and 100 healthy subjects were investigated in the study. Genotype and allele distributions of rs3850641, rs1234313, and rs10912580 polymorphisms in the promoter region of the gene were investigated by polymerase chain reaction-restriction fragment length polymorphism. In addition, haplotype frequencies estimation and linkage disequilibrium analysis were performed by SNPStats web tool. ResultsThe distribution of AA, AG and GG genotypes of rs3850641 was significantly different between the patient and healthy groups (P = 0.009). In addition, frequencies of A and G alleles of rs3850641 were different between the groups (P < 0.001). Also the distribution of rs3850641 genotypes was different between the women of the both groups (P = 0.007). Our analysis revealed that rs3850641 AG (Odds ratio = 0.393, 95 % confidence interval = 0.170–0.907, P = 0.029) and GG (Odds ratio = 0.373, 95 % confidence interval = 0.168–0.830, P = 0.016) genotypes were associated with decreased risk of the disease. However, rs1234313 genotype and allele distributions were not different between the groups. The distribution of rs10912580polymorphism. AA, AG, and GG genotypes was significantly different between the groups (P = 0.007). rs10912580 AG genotype was associated with low risk of the disease (Odds ratio = 0.252, 95 % confidence interval = 0.102–0.623, P = 0.003). The distribution of haplotypes was statistically different between the patient and healthy groups (P < 0.001). A-G-A was the most frequent haplotype among the patients and the estimated frequency was higher than that of the control group (0.5527 versus 0.3739). ConclusionThe distribution of rs3850641 and rs10912580 genotypes was different between the patients and healthy subjects. Moreover, rs3850641 AG and GG genotypes and also rs10912580 AG genotype were associated with low risk of the disease in Iranians. Further studies with large groups are recommended to show whether genotype variation in the patients could alter the response to treatment or not.

Association of Tenascin-C Gene Polymorphisms with Risk of Acute Coronary Syndrome in South Indian Population: A Case-Control Genetic Association Study.

Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

The Association of M235T Genetic Polymorphism in Angiotensinogen Gene and Other Non-Genetic Factors with Essential Hypertension among Jordanian Patients.

Hypertension, characterized by elevated pressure, poses a significant health risk. Recent studies in Jordan highlight high hypertension rates, emphasizing the need for genetic investigations to comprehend essential hypertension determinants. The AGT gene, part of the Renin Angiotensin System, is linked to blood pressure regulation. Limited information exists on the frequency of this polymorphism among Jordanian hypertensive patients. This study explores the association between the AGT M235T polymorphism and essential hypertension in Jordan. A cross-sectional study with 435 participants (199 hypertensive, 236 non-hypertensive) was conducted at the University of Jordan Hospital. Blood pressure was measured, and genetic analysis of the AGT M235T polymorphism was completed using the PCR-RFLP technique. Chi-square and t-tests were used for comparisons using SPSS software. Hypertensive patients exhibited significantly higher weight, BMI, and blood pressure. Genotyping results showed no significant difference (p > 0.05, Chi-square) in AGT M235T polymorphism distribution between control and patient groups. In addition, allele frequencies showed comparable patterns (p > 0.05, Chi-square). All genotype frequencies showed no deviation from the Hardy-Weinberg equation (p > 0.05, Chi-square). The AGT M235T genetic polymorphism is not more prevalent among hypertensive patients in Jordan, although the average weight and BMI among hypertensive patients is higher than the non-hypertensive participants. Obesity can be addressed as a potential risk factor for essential hypertension in Jordan. In addition, it is recommended to find out the influence of the AGT M235T genetic polymorphism on the response of antihypertensive drugs among hypertensive patients in Jordan.

Association of the rs1801133 and rs1801131 polymorphisms in the MTHFR gene and the adverse drug reaction of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients

Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it’s the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect. Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G&amp;gt;A and rs1801131T&amp;gt;G) on the adverse drug reaction for RA Iraqi patients. Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patients were divided according to the occurrence of adverse drug reactions. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was being utilized for MTHFR variants (rs1801133 and rs1801131). The Macrogen Company (Korea) provided the forward and reverse primers in lyophilized form. All PCR procedures are carried out using a PCR thermal cycler (Germany). Results: The study included 95 patients with RA, with a mean age of 43.1 ± 10.6 years, most of the patients were female (85.3%), about 35.8% were smokers, most of the patients had disease low activity (45.2%), followed by moderate (41.1%), high (9.5%), and remission (4.2%). No significant association between individual genetic polymorphism with adverse drug reactions. AG haplotype for rs1801133 rs1801131 polymorphism is associated with reducing the risk of overall adverse drug reactions, meanwhile, GT haplotype for rs1801133, and rs1801131 polymorphism were marginally associated with increased risk of adverse drug reactions. Conclusion: In conclusion, we have successfully found a panel of pharmacogenetic indicators that have the potential to be valuable in predicting the response to methotrexate treatment in patients with rheumatoid arthritis. Haplotypes for rs1801133 rs1801131 polymorphism are associated with reducing or increasing the risk of MTX adverse drug reactions. It is very important to evaluate patients’ haplotypes before starting the therapy program so that we can expect the treatment outcome with the most suitable dose and most tolerable one at the same time.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

BackgroundThe majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring.MethodsA multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions.ResultsThere was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed.ConclusionsThe polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

The Influence of Genetic Polymorphic Variability of the Catechol-O-methyltransferase Gene in a Group of Patients with a Diagnosis of Behavioural Addiction, including Personality Traits.

Gambling Disorder (GD) is characterised by a harmful, enduring, and recurrent involvement in betting-related behaviours. Therefore, GD shares similar biological mechanisms and symptoms to substance use disorders (SUD). Therefore, in this study, we chose the behavioural addictions group. During the examination and recruitment to the study, it turned out that all the people undergoing treatment for gambling addiction were also addicted to amphetamines, which is consistent with the biological mechanism related to cerebral neurotransmission. The aim of the study was to investigate the association of the COMT gene polymorphism with behavioral addiction. The study group consisted of 307 participants: 107 men with gambling disorder and amphetamine dependency (mean age = 27.51, SD = 5.25) and 200 non-addicted, nor dependent, free from neuro-psychiatric disorders control group men (mean age = 20.20, SD = 4.51). Both groups were subjected to psychometric evaluation using the State-Trait Anxiety Inventory and the NEO Five-Factor Personality Inventory. Genomic DNA was extracted from venous blood following standard protocols. Determination of the rs4680 polymorphism in the COMT gene was performed using the real-time PCR technique. Statistically significant differences in the frequency of rs4680 genotypes were found in the tested sample of subjects compared with the control group (p = 0.03543). Subjects with gambling disorder and amphetamine use disorder compared to the control group obtained higher scores in the assessment of the STAI trait scale (p = 0.0019), state scale (p < 0.0000), and NEO-FFI Neuroticism scale (p < 0.0000). Significantly lower results were obtained for the NEO-FFI Agreeability scale (p < 0.0000). Additionally, a significant statistical impact of gambling disorder and amphetamine use disorder, and the COMT rs4680 genotype was demonstrated for the score of the STAI trait (p = 0.0351) and state (p = 0.0343) and the NEO-FFI Conscientiousness scale (p = 0.0018). We conclude that COMT and its polymorphic variant influence the development of addiction. Still, considering its multifactorial and polygenic nature, it should be combined with other factors such as personality.

The Association of ADAMTS7 Gene Polymorphisms with the Risk of Coronary Artery Disease Occurrence and Cardiovascular Survival in the Polish Population: A Case-Control and a Prospective Cohort Study.

The aim of this study was to investigate whether the polymorphisms of the ADAMTS7 gene affect the risk of occurrence and mortality due to CAD. The study group included 231 patients diagnosed with CAD and 240 control blood donors. The genotyping of specified polymorphisms, i.e., rs1994016, rs3825807, and rs7173743, was performed using the TaqMan-PCR. We found that the C allele carriers of the rs1994016 and A allele carriers of the rs3825807 polymorphisms increased the risk of CAD, respectively: OR = 1.72, p = 0.036; OR = 1.64, p = 0.04. Moreover, we studied the biological interactions of specified variants, i.e., rs3825807, rs1994016, and rs7173743, and previously approved risk factors of CAD. We demonstrated here that selected polymorphisms of ADAMTS7 increased the risk of CAD altogether with abnormalities of total cholesterol and LDL concentrations in serum. Although survival analyses did not reveal statistical significance, we observed a trend for the AA genotype of the rs3825807 ADAMTS7, which may predispose to death due to CAD in a 5-year follow-up. In conclusion, the ADAMTS7 polymorphisms investigated in this study may increase the risk of occurrence and/or death due to CAD in the Polish population.

Association of polymorphisms in TLR3 and TLR7 genes with susceptibility to COVID-19 among Iranian population: a retrospective case-control study.

Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main factors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibility to COVID-19 in a sample of the Iranian population. This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was genotyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a significant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P<0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167). SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis

ABSTRACT Background This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). Methods This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. Results Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503–0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110–1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. Conclusion Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease

To assess the association between the polymorphism of integral protein α4 (ITGA4) and intercellular adhesion molecule 1 (ICAM-1) genes and the risk and clinicopathological characteristics of Crohn's disease (CD) among Chinese patients. From January 2010 to January 2021, a total of 215 CD patients and 529 gender- and age-matched healthy controls were enrolled from the Second Affiliated Hospital of Wenzhou Medical University as the study subjects. Genotypes of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) were determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Harvey-Bradshaw Index (HBI) was applied to assess the disease activity of CD, and the patients were further divided into subgroups based on the Montreal Classification Criteria of CD. Unconditional logistic regression was employed to analyze the distribution of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) polymorphisms between the patients and healthy controls and their association with the clinicopathological characteristics of the patients. The frequencies of T allele and CT+TT genotypes of ITGA4 (rs7562325) were higher in CD patients than the healthy controls (40.70% vs. 31.57%, P = 0.001; 62.79% vs. 54.36%, P = 0.042). The G variant and AG+GG genotypes of ITGA4 (rs6740847) were less common in patients with moderately to severely active CD compared with those with mildly active CD (31.18% vs. 51.72%, P = 0.002; 55.91% vs. 75.86%, P = 0.042). However, the opposite conclusion was drawn for the G allele (G) and AG+GG genotypes of ICAM-1 (rs5498) (31.45% vs. 17.24%, P = 0.027; 54.30% vs. 31.04%, P = 0.020). Compared with patients with terminal ileal or ileocolic CD, G allele and AG+GG genotypes of ITGA4 (rs6740847) were more prevalent in patients with colonic CD (55.26% vs. 29.38%, P < 0.001; 84.21% vs. 53.11%, P<0.001). The same conclusion could also be drawn for the G allele and AG+GG genotypes of ICAM-1 (rs5498) (42.11% vs. 26.84%, P = 0.008; 73.69% vs. 46.33%, P = 0.002). The frequency of homozygous GG genotype of ICAM-1 (rs5498) was lower in patients with stricturing and penetrating CD than those with non-stricturing and non-penetrating CD (0.00% vs. 12.32%, P = 0.001). The G allele and AG+GG genotypes of the ITGA4 (rs6740847) were more common in patients with perianal lesions than those without (40.28% vs. 30.77%, P = 0.049; 72.22% vs. 51.75%, P = 0.004). Variants of the ITGA4 (rs7562325) may be a risk factor for CD, whilst those of the ITGA4 (rs6740847) may be associated with the decline of disease activity and risk for colon involvement and perianal lesions. Variants of the ICAM-1 (rs5498) may increase the risk of disease activity and colonic involvement in CD patients, however, it may be a protective factor for stenosis and penetration. In addition, variants of the ITGA4 (rs6740847) and ICAM-1 (rs5498) may be associated with the early onset of CD.

The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study)

Several studies have shown association of single nucleotide polymorphisms (SNPs) of hepcidin regulatory pathways genes with impaired iron status. The most common is in the TMPRSS6 gene. In Africa, very few studies have been reported. We aimed to investigate the correlation between the common SNPs in the transmembrane protease, serine 6 (TMPRSS6) gene and iron indicators in a sample of Egyptian children for identifying the suitable candidate for iron supplementation.Patients and methods One hundred and sixty children aged 5–13 years were included & classified into iron deficient, iron deficient anemia and normal healthy controls. All were subjected to assessment of serum iron, serum ferritin, total iron binding capacity, complete blood count, reticulocyte count, serum soluble transferrin receptor and serum hepcidin. Molecular study of TMPRSS6 genotyping polymorphisms (rs4820268, rs855791 and rs11704654) were also evaluated.Results There was an association of iron deficiency with AG of rs855791 SNP, (P = 0.01). The minor allele frequency for included children were 0.43, 0.45 & 0.17 for rs4820268, rs855791 & rs11704654 respectively. Genotype GG of rs4820268 expressed the highest hepcidin gene expression fold, the lowest serum ferroportin & iron store compared to AA and AG genotypes (p = 0.05, p = 0.05, p = 0.03 respectively). GG of rs855791 had lower serum ferritin than AA (p = 0.04), lowest iron store & highest serum hepcidin compared to AA and AG genotypes (p = 0.04, p = 0.01 respectively). Children having CC of rs11704654 had lower level of hemoglobin, serum ferritin and serum hepcidin compared with CT genotype (p = 0.01, p = 0.01, p = 0.02) respectively.Conclusion Possible contribution of SNPs (rs855791, rs4820268 and rs11704654) to low iron status.

Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin

Among the congener of dioxin, 2,3,7,8-TCDD is the most toxic, having a serious long-term impact on the environment and human health. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in the detoxification and excretion of endogenous and exogenous lipophilic compounds, primarily in the liver and gastrointestinal tract. This study aimed to investigate the association of UGT1A1 gene polymorphisms, expression levels, and enzyme concentration with Agent Orange/Dioxin exposure. The study included 100 individuals exposed to Agent Orange/Dioxin nearby Da Nang and Bien Hoa airports in Vietnam and 100 healthy controls. UGT1A1 SNP rs10929303, rs1042640 and rs8330 were determined by Sanger sequencing, mRNA expression was quantified by RT-qPCR and plasma UGT1A1 concentrations were measured by ELISA. The results showed that UGT1A1 polymorphisms at SNPs rs10929303, rs1042640 and rs8330 were associated with Agent Orange/Dioxin exposure (OR = 0.55, P = 0.018; OR = 0.55, P = 0.018 and OR = 0.57, P = 0.026, respectively). UGT1A1 mRNA expression levels and enzyme concentration were significantly elevated in individuals exposed to Agent Orange/Dioxin compared to controls (P < 0.0001). Benchmark dose (BMD) analyses showed that chronic exposure to 2,3,7,8-TCDD contamination affects the UGT1A1 mRNA and protein levels. Furthermore, UGT1A1 polymorphisms affected gene expression and enzyme concentrations in individuals exposed to Agent Orange/Dioxin. In conclusion, UGT1A1 gene polymorphisms, UGT1A gene expression levels and UGT1A1 enzyme concentrations were associated with Agent Orange/Dioxin exposure. The metabolism of 2,3,7,8-TCDD may influence UGT1A gene expression and enzyme concentrations.

Association of single nucleotide polymorphisms in the F2RL1 gene with clinical and inflammatory characteristics of patients with asthma

BackgroundProteinase-activated receptor 2 (PAR-2) is a G-protein coupled receptor associated with many inflammatory diseases, including asthma. We have shown an association between PAR-2 expression in peripheral blood monocytes and asthma severity as well as blood PAR-2 mRNA level and lung function. Since F2RL1 (the gene encoding PAR-2) polymorphisms affect PAR-2 expression, we hypothesize they may affect asthma severity.MethodsWe recruited 76 subjects with asthma of varying severity and collected clinical (FEV1 [% predicted], FEV1/FVC, IgE) and immunological (PAR-2 mRNA, blood eosinophils) disease parameters. We also genotyped these individuals for 3 F2RL1 SNPs (-45C/T, -149C/G, c.621C/T).ResultsWe found that the F2RL1 SNP “C” allele of -45C/T (rs1529505) was associated with PAR-2 mRNA and blood eosinophils. F2RL1 SNP c.621C/T (rs631465) was associated with PAR-2 mRNA. The F2RL1 SNP -149C/G (rs2242991) had no association with any of the parameters studied. This study identified one F2RL1 SNP rs1529505 is associated with parameters of asthma, but not asthma severity.ConclusionLarger studies are needed to further elucidate the role of PAR-2 in the pathophysiology of asthma and the influence of genetic variation.

Association of Cytokine IL-17, IL-4, IL-6, and IL-12 Gene Polymorphisms in Rheumatoid Arthritis Patients in a Tertiary Care Hospital in Bangladesh.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves cytokines in its pathogenesis. This study is aimed at investigating if gene polymorphisms in cytokines like IL-17, IL-4, IL-6, and IL-12 affect RA susceptibility and severity in the Bangladeshi population. This was a cross-sectional comparative study that included 40 diagnosed RA patients according to the American College of Rheumatology (ACR) criteria 2010, who were free from other rheumatological diseases, and 40 healthy subjects for comparison. The study used PCR-RFLP to determine the IL-17, IL-4, IL-6, and IL-12 cytokine gene polymorphisms. Patients had a mean age of 37.22 ± 6.70 years. Among the patients, 31 were female and 9 were male. The mean disease duration was 18.11 ± 7.39 months. The study found that rheumatoid arthritis patients with the IL-17F (7488 A/G) polymorphism with GG genotype (P = 0.006, OR = 8.56, 95% CI = 1.77 - 41.33) and IL-12B (1188 A/C) polymorphism with AC (P = 0.012, OR = 3.69, 95% CI = 1.43 - 9.53) and CC (P = 0.013, OR = 7.58, 95% CI = 1.56 - 36.88) genotypes were significantly associated with disease risk. Furthermore, patients with the IL-17F (7488) GG genotype and IL-12B (1188) AC and CC genotypes had higher rheumatoid arthritis disease severity and activity parameters. The study found no significant association between polymorphisms involving IL-4 (590 C/T) and IL-6 (174 G/C) genes and rheumatoid arthritis disease risk in the Bangladeshi population. Gene polymorphisms in cytokines IL-17F (7488 A/G) and IL-12B (1188 A/C) can predict disease susceptibility and severity in Bangladeshi rheumatoid arthritis patients.

Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.