Distribution Of Alleles Research Articles

Association between the ARMS2 rs10490924 risk genotype and dry-age related macular degeneration patients with and without reticular pseudodrusen in a Turkish population: findings from a study conducted at a tertiary clinic.

To evaluate the relationship between the presence of reticular pseudodrusen (RPD) and the risk allele of ARMS2 rs10490924 variation in dry-AMD patients by using multimodal imaging. Also, to compare patients with and without RPD and healthy volunteers according to the distribution of the risk allele. In this cross-sectional study, dry-AMD patients with (Group A,n = 50) and without (Group B,n = 50) RPD and healthy volunteers (Group C,n = 50) were enrolled. After detailed ophthalmologic examination, confocal scanning laser ophthalmoscope (Heidelberg, Germany) was used to acquire near infra-red (NIR) imaging for RPD and the diagnosis was confirmed by Spectral Domain-Optical coherence tomography (Heidelberg, Germany). In silent choroidal neovascularization suspicion, optical coherence tomography angiography (Optovue, Fremont, CA) was performed and those were excluded. For genetic assessment, peripheric blood sampling was performed. Using next-generation sequencing technique (NGS), ARMS2 rs10490924 single nucleotide polymorphism was investigated. Groups were compared according to the distribution of the risky allele. 150 eyes of 150 participants were included. In Group A, 42% (21) of patients were heterozygous for the T risk allele, 30% (15) were homozygous, and the risk allele was not detected in 28% (14). In Group B, 44% (22) of patients were heterozygous, 17% (8) were homozygous, and the risk allele was not detected in 39% (20). In Group C, 30% (15) of participants were heterozygous, 4% (2) were homozygous, and variation was not observed in 64% (32). Homozygous participants in Group A were significantly higher than other two groups (Group A-B: OR = 2.67, 95% CI: 0.895, 8.020; Group A-C: OR = 17.14, 95% CI: 3.449, 85.208) while in Group B, homozygous individuals were higher than Group C (respectively, p values 0.0039, 0.0002, 0.013). T risky allele frequencies were 51%, 38%, and 20% in Groups A, B, and C, respectively, which was significantly higher in Group A (p = 0.02). Genetic influence in AMD is inevitable while certain differences according to different ethnicities may apply. Association of genetic variations and imaging findings like RPD is lacking among literature for different populations. By the aspect of this study, the relationship between RPD and ARMS2 rs10490924 polymorphism in dry-AMD patients were highlighted among Turkish population by using multimodal imaging for the first time. What is Known? Pathophysiology of age-related macular degeneration is influenced from multiple factors including single nucleotide polymorphisms. The variations of ARMS2 are suspected well in the current literature. Reticular pseudodrusen is related to advanced stages of age related macular degeneration disease. What is New? The ARMS2 rs10490924 risk genotype is associated with the presence of reticular pseudodrusen in dryage related macular degeneration patients. Homozygous genotype of T risk allele is evaluated significantly higher in dry age related macular degeneration patientswith reticular pseudodrusen.

Clinical and neurological specifics of the vertebrogenic lumbosacral radiculopathy course in the patients with RS1143627 polymorphism of the <i>IL-1β</i> gene

Rationale: Vertebrogenic lumbosacral radiculopathy (VLSRP) is a consequence of exposure to physical exertion, back injuries, and smoking. Genetic polymorphism of the cytokine IL-1β contributes to the progression of VLSRP due to its increased production in certain genetic variants. Aim: To establish an association between the rs1143627 polymorphism of the IL-1β gene with VLSRP, as well as with clinical and neurological specifics of VLSRP during its treatment. Methods: The study involved 121 patients with VLSRP aged 22 to 66 years (median, 41 [35; 49] years; men, 110 (90.91%)), treated in the in-patient Department of Neurology from January 2023 to February 2024, and 100 age- and gender compatible healthy subjects. Based on the results of clinical and neurological assessments, the indices of the Digital Rating Scale, Oswestry and Roland-Morris questionnaires were determined. The rs1143627 polymorphism was identified by real-time polymerase chain reaction (IQ5 amplifier (Bio-Rad, USA)) with the SNP-express (IL-1β-31C/T) test system (Litech, Russia). Results: VLSRP was associated with the distribution of alleles (χ2 = 3.93; p = 0.049) and genotypes according to the dominant model (χ2 = 4.7; p = 0.032) of the rs1143627 polymorphism of the IL-1β gene. The minor T allele increased the odds ratio for VLSRP (OR 1.51; 95% CI 1.004–2.26) in the dominant model; the sum of CC + CT genotypes was also associated with increased VPSRP odds ratio (OR 1.814; 95% CI 1.056–3.115). The DRS scores under treatment showed the significant predominance of pain in the T (CT + TT) allele carriers (p 0.001). As assessed by the Oswestry and Roland-Morris questionnaires, the minor T allele in CT + TT genotypes demonstrated prevailing everyday life activities and less effective results after a treatment course (p 0.001). In the study subjects of ≤ 41 years of age, the multiplicative model showed a higher risk of VLSRP with the minor T allele by 1.8-fold (OR 1.80; 95% CI 1.02–3.19). In the dominant model, the sum of genotypes with the minor T allele (CT + TT) was associated with a 2.23-fold higher risk of VLSRP (OR 2.23; 95% CI 1.05–4.72). Conclusions: We were able to find the association between the rs1143627 polymorphism of the IL-1β gene with VLSRP, with a higher risk of the disease in the patients of ≤ 41 years of age, higher DRS, Oswestry, and Roland-Morris questionnaire scores, which was related to the presence of a minor T allele and CT + TT genotypes.

Clinical and Laboratory Characteristics of Pediatric Patients With ACKR1/DARC-Associated Neutropenia.

ACKR1/DARC-associated neutropenia (ADAN), resulting from homozygosity for a single nucleotide polymorphism (SNP) in the ACKR1/DARC gene (rs2814778), is a common cause of benign neutropenia that primarily affects individuals of African and Jewish Yemenite descent. We aimed to characterize ADAN in pediatric patients in Israel, given its ethnically diverse population. We assessed children with isolated neutropenia treated during 2018-2023 at one pediatric center, for the ACKR1/DARC polymorphism, using Sanger sequencing or targeted next-generation sequencing. Of 115 patients evaluated, 49 (42.6%) were diagnosed with ADAN; of these, 29 (59%) had absolute neutrophil counts in the severe range (0-0.5×109/L) at diagnosis. The allele distribution revealed 37% of Muslim Arab and 61% of Jewish origin. Yemenite, Ethiopian, Mediterranean, Asian, and European ancestry were included; 59% had a family history of neutropenia. The median age at the first neutropenia detection was 1.2years; 91.8% were identified during routine blood counts. The median absolute neutrophil count at diagnosis was 0.5×109/L (interquartile range: 0.3). An increased susceptibility to infections was not found either before or during the median follow-up period of 2.5years (interquartile range: 1.54) after the diagnosis of ADAN. In 34 patients (72.3%), neutrophil counts were in the normal range during febrile illnesses. We identified ADAN in individuals of variable ethnicities, almost half with severe neutropenia. We recommend testing for ADAN in all children with isolated neutropenia without severe infections. Homozygosity for the ACKR1/DARC rs2814778 SNP may obviate the need for further investigation, follow-up, or treatment in specific clinical scenarios.

Hepatocyte nuclear factor 1 alpha variants as risk factor for hepatocellular carcinoma development with and without diabetes mellitus

BackgroundHNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC. ObjectiveTo evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in hepatitis C virus (HCV)-infected patients. Subjects and methodsThis study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants. ResultsThe frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC + DM) was significantly higher compared to the control group (P = 0.006, P = 0.018, P < 0.001 respectively). The combined dominant model (AA + GA) of rs 2464196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC + DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC + DM (73 %) compared to the group of DM or HCC patients. In contrast, the HNF1A rs1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions. ConclusionThis finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs1169310 polymorphism was of no significance as a risk factor in the current study. However, as we limited our study to Egyptian participants, more research on other ethnic groups would be required. Also, large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.

Impact of the COL1A1 (RS1107946) gene polymorphism on anterior cruciate ligament rupture in professional soccer players

Objectives To describe the allelic frequency of rs1107946, belonging to the COL1A1 gene in professional soccer players and compare these findings with data from continental populations described in the 1000 Genomes database, in order to evaluate the frequency of genotypes highly associated with genetic susceptibility to anterior cruciate ligament (ACL) injuries in the literature. Methods The DNA of the 38 professional soccer players was collected from oral mucosa samples. DNA extraction was performed using the PureLinkTMGenomicDNAMini Kit, according to the manufacturer's protocol. For genotyping and allelic discrimination of the selected SNP (rs1107946), real-time PCR was used with TaqMan® SNP GenotypingAssay specific probes (AppliedBiosystems, Foster City, CA, USA) on the QuantStudio 6 Flex Realtime PCR system. The MMA was consistently identified in all specimens. In 26 of 33 (82%) specimens, the MMA branched directly from the popliteal artery, while in 6, the MMA shared a common trunk with the inferior medial genicular artery (IMGA). The MMA was easily distinguishable from the superior MGA, inferior MGA, and MGA, given its direct course to the medial joint line with terminal branches to the posterior horn of the medial meniscus and deep to the semimembranosus tendon. The MMA exhibited a smaller vessel diameter relative to the genicular arteries. Results Our findings demonstrated that the frequency of the wild-type allele C was 65%, while the frequency of the mutant allele A was 45%, highlighting that despite the wild-type allele, which confers protection against the risk of ACL injury, is predominantly distributed in the sample, the mutant allele is significantly present in the individuals investigated. When comparing our findings with data from continental populations described in 1000 Genomes, we found statistically significant allelic and genotypic distributions (Student's T Test p = 0.021), demonstrating that the athletes investigated have a different genetic profile. In our findings, the individuals studied presented a statistically significant allelic frequency of the mutation when compared to the European population, inferring that the frequency of this mutation is higher in European individuals than in mixed-race individuals from Brazil. Conclusion The prevalence of the rs1107946 polymorphism of the COL1A1 gene in athletes may have an important role in the development of ACL injuries.

Microsatellite Markers & Mitochondrial D-Loop Based Phylogenetic And Diversity Analysis In Gabrali Cattle.

The Gabrali cattle is a multipurpose breed, native to Khyber Pakhtunkhwa, Pakistan. Despite its economic importance, scientific data about its phylogeny and genetic diversity is scarce. To address this issue, the present study was conducted on thirty (30) unrelated Gabrali male and female animals, from which blood samples were collected and DNA was extracted. Twelve (12) microsatellite loci and 1159bp of D-loop region were amplified via PCR and visualized on a 2% agarose gel. Sanger sequencing technique was used to sequence the D-loop amplicons. The microsatellite loci revealed 83 alleles with MNA (mean no of alleles per locus) = 8.8, the Ho (observed heterozygosity) and He (expected heterozygosity) of all loci were 0.58 and 0.50 respectively, mean PIC (Polymorphic Information content) = 0.59 and FIS (Inbreeding coefficient) = 0.056 using GeneAlEx® software. Microsatellite analysis revealed a normal allelic distribution across the breed, consistent with Hardy-Weinberg equilibrium. D-loop sequencing revealed eight haplotypes with 30 SNPs using DNA SP 6.0 software. High AT content was observed than GC content i.e. 55.9% and 44.1% respectively, while the transition to transversion ratio was R = 10:1. The value of Haplotype and Nucleotides diversity was Hd = 0.8601 ± SD = 0.0895 and Π = 0.0136 ± SD = 0.00197 respectively. Phylogenetic analysis done using Neighbor-joining method with bootstraps value of 1000, revealed the monophyletic clade of both Gabrali and Bos indicus haplotypes. Furthermore, the introgression of genes from national cattle breeds into Gabrali cattle was observed. It is concluded that Gabrali cattle have common ancestry with Bos indicus having no threats of genetic bottleneck having substantial genetic diversity.

The effect of VEGF and KDR gene variants on Crimean-Congo hemorrhagic fever

Background Crimean-Congo hemorrhagic fever (CCHF), an acute viral hemorrhagic fever disease, has a high mortality rate among humans. Hemorrhagic propensity is caused by coagulation malfunction and increased capillary permeability brought on by the resultant vascular injury. Vascular endothelial growth factor (VEGF) and VEGF receptor-2, or KDR (kinase insert domain containing receptor), are effective in vasculogenesis and angiogenesis. CCHF was stated to have endothelial dysfunction. This study aimed to evaluate whether the VEGF and KDR gene variants contribute to the development of CCHF in the Turkish population. Methods A total of 101 subjects, including 51 CCHF patients and 50 healthy controls, were included in the study. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype VEGF 936 C > T (rs3025039) and KDR − 604 T > C (rs2071559) variants. The results were statistically analyzed. Results The VEGF 936 C > T genotype and allele distributions did differ significantly between the patients and the controls. The subjects carrying the C/C genotype and C allele had a higher risk of developing CCHF than the control group (p˂0.05). There was a statistically significant association between the controls and the patients in terms of VEGF 936 C > T C/C versus C/T + T/T (p˂0.05, OR:3.273, 95%Cl: 1.44–7.63). The KDR − 604 T > C variant’s allele and genotype distribution were not significantly different between the patients and controls. Conclusion This study suggests the VEGF 936 C > T variant is a genetic marker of sensitivity to CCHF among the Turkish population and may help protect against the disease.

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI] 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

EDNRA affects susceptibility to large artery atherosclerosis stroke through potential inflammatory pathway

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway.

Association between rs8192678 C/T polymorphism of the PPARGC1A gene and metabolically associated fatty liver disease in obese children living in the Moscow region

Over the past 30 years, the incidence of childhood obesity has quadrupled, leading to a rise in metabolically associated fatty liver disease (MAFLD), which has multifactorial genesis. Numerous studies highlight a significant genetic contribution to the development and severity of MAFLD. Purpose of the study. Тo determine the distribution of alleles and genotypes of the rs8192678 C/T polymorphism of the PPARGC1A gene and its relationship with the development of MAFLD in obese children living in the Moscow region. Materials and methods. The study included 87 children with exogenous constitutional obesity. The children were divided into two groups: group I - obesity without MAFLD (n = 43), group II - obesity with MAFLD (n = 44). The association of genotypes with the risk of developing MAFLD was studied in various genetic models. Results. 43 (49.4%) children had genotypes containing the T allele: 4 (4.6%) - homozygous TT genotype, 39 (44.8%) - heterozygous CT genotype. The CC genotype was detected in 44 (50.6%) children. The frequency of allele C was 73%. Carriers of the T allele have almost twice the risk of developing MAFLD than сarriers of the C allele (OR = 2.08 (95% CI: 1.05-4.24), p = 0.041). Conclusion. Тhe rs8192678 polymorphism increases the risk of developing MAFLD already in childhood, and with the homozygous TT genotype, this risk more than doubles. Studying the genetic contribution to the development of MAFLD enables a comprehensive approach to assessing individual risks of each patient.

Frequency Distributions of Alleles and Genotypes and Lung Cancer Risk of Polymorphisms DCK, SLC29A1, and SLC29A3 in South Indian Healthy Population.

Introduction Gemcitabine, a cytotoxic drug, is used to treat a variety of solid tumors, such as pancreatic, lung, and breast malignancies. The efficiency rates for gemcitabine have decreased due to an increase in genetic instability. The association between gene polymorphisms and the efficacy of gemcitabine therapy may be better known by understanding the intricacies of genetics that target a few or more genes in drug-targeting metabolic pathways. Moreover, several studies have documented differences in the therapeutic response among various ethnicities to gemcitabine chemotherapy. Therefore, the purpose of this study was to determine the normative frequencies of gene polymorphisms linked to the metabolic pathway of gemcitabine (DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776)) in Southern part of Indian healthy population and compared it with the 1000 genome population. In addition, the association of the above single nucleotide polymorphisms (SNPs) with lung cancer susceptibility was also evaluated. Methods The present study used real-time polymerase chain reaction (RT-PCR) for performing genotyping in 184 healthy participants as well as 123 South Indian patients with lung cancer. The frequencies of alleles and genotypes of the aforementioned genetic variants were in Hardy-Weinberg equilibrium (p > 0.05). Results The minor allele frequencies (MAF) of the SNPs DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1+913C>T (9394992), SLC29A3 +4967C>A (10999776) were 3.8%, 17.7%, 27.7%, 29.3% respectively in healthy population. The MAF of the SNPs, DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776) in lung cancer patients was 2%, 15%, 23.2%, and 24.4% respectively. A trend toward a protective effect against lung cancer was observed with SLC29A1 +913C>T (9394992). Conclusion The observed frequencies of alleles and genotypes in the South Indian population were significantly different as compared to the 1000 genome population. In the present study, an association of SLC29A1 rs9394992 C>T between lung cancer patients and healthy subjects showed a trend toward protective effect against lung cancer risk.There was no association found between the other studied SNPs and lung cancer risk.

A study of granulysin and pentraxin 3 genetic polymorphisms and their contribution to acne susceptibility.

This study aims to examine the genetic polymorphisms of the granulysin (GNLY) and pentraxin 3 (PTX3) genes and their association with acne in Egypt. Acne vulgaris is classified as a disorder of the pilosebaceous unit. Clinical, histological, and immunological findings indicate that inflammation is involved in every stage of acne development. GNLY and PTX3 are both involved in the body's immune system and may play a role in the pathophysiology of acne. This case-control study included 180 participants who have acne and 180 healthy controls. Real-time PCR was used to genotype GNLY rs7908 and PTX3 rs2305619 polymorphisms. Genotype occurrence and allelic spreading for both single nucleotide polymorphisms (SNP) are in Hardy-Weinberg equilibrium. Regarding rs7908, no statistical difference was observed in the genotype and allele distributions between acne patients and controls. On the other hand, rs2305619 showed a statistical difference in the genotype and allele distributions between acne patients and controls, with a marked prevalence of the GG group and G allele in acne patients. Our study revealed a significant link between the PTX3 rs2305619 and acne susceptibility in Egypt, with the AG + GG genotype strongly predicting acne. In contrast, the GNYL rs7908 polymorphism was not associated with acne. These results highlight a genetic component to acne and suggest that PTX3 rs2305619 could be a key marker for understanding acne susceptibility.

Population genetic dissection of HLA-DPB1 amino acid polymorphism to infer selection

Although allele frequency data for most HLA loci provide strong evidence for balancing selection at the allele level, the DPB1 locus is a notable exception, with allele frequencies compatible with neutral evolution (genetic drift) or directional selection in most populations. This discrepancy is especially interesting as evidence for balancing selection has been seen at the nucleotide and amino acid (AA) sequence levels for DPB1. We describe methods used to examine the global distribution of DPB1 alleles and their constituent AA sequences. These methods allow investigation of the influence of natural selection in shaping DPβ diversity in a hierarchical fashion for DPB1 alleles, all polymorphic DPB1 exon 2-encoded AA positions, as well as all pairs and trios of these AA positions. In addition, we describe how asymmetric linkage disequilibrium for all DPB1 exon 2-encoded AA pairs can be used to complement other methods. Application of these methods provides strong evidence for the operation of balancing selection on AA positions 56, 85–87, 36, 55 and 84 (listed in decreasing order of the strength of selection), but no evidence for balancing selection on DPB1 alleles.

Association between ATG16L1 rs2241880(T300A) and rs4663421 and ANCA‑associated vasculitis in the Guangxi population of China: Propensity score matching analysis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rare autoimmune disease with an unclear pathogenesis. The present study investigated the associations between autophagy-related protein 16-like 1 (ATG16L1) rs2241880(T300A) and rs4663421 and AAV. A total of 177 patients with AAV and 216 healthy controls were included. Propensity score matching was used to match the two groups of subjects in terms of sex, age and ethnicity. Analyses of the relationships between these genetic polymorphisms and AAV susceptibility, including comparisons of allele and genotype frequency distribution, linkage disequilibrium analysis and analysis of single nucleotide polymorphism (SNP) interactions between two loci were performed. The association between the loci and laboratory test results and renal pathology were also analysed. A total of 154 pairs of patients with AAV and healthy controls was successfully matched. Neither polymorphism was associated with AAV susceptibility. However, SNP interaction in the model constructed with the two loci was statistically significant (P=0.018), and the combination of the AA genotype of rs2241880(T300A) and GG genotype of rs4663421 was associated the highest disease risk. The differences in the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP) levels and 24-h urine protein level between patients with the rs2241880(T300A) AA + AG genotypes and the GG genotype were statistically significant (P<0.05). Furthermore, significant differences in the severity of glomerulosclerosis and global sclerosis were detected between individuals with the AA + AG genotype and those with the GG genotype at the rs2241880(T300A) locus (P<0.05). Similarly, there were statistically significant differences in degree of segmental sclerosis between individuals with CC + CG genotypes and those with GG genotypes at the rs2243421 locus (P<0.05). In summary, the single gene polymorphisms of these loci were not associated with genetic susceptibility to AAV. However, SNP interactions may serve a role in the risk of AAV. The rs2241880(T300A) polymorphism may be associated with BVAS, CRP levels and 24-h urine protein level in AAV. These SNPs may be associated with glomerulosclerosis and segmental sclerosis.

HLA-B allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

We utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature. The distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals. Our study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.

Polymorphism of RAAS genes in patients with COVID-19: comparison with frequency in population and relationship with severity of course

Evaluation of genes polymorphisms frequencies of angiotensinogen (AGT), angiotensin converting enzyme type 1 (ACE1) and angiotensin II receptors type 1 (AGTR1) and type 2 (AGTR2) in patients admitted with coronavirus disease (COVID-19) and its association the severity of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2). The study included 100 patients admitted to the hospital with a laboratory-confirmed diagnosis of COVID-19. All patients were identified with alleles and genotypes of polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene. The frequencies of each polymorphisms were compared with population. Statistical processing was performed using the Statistica 8.0 software package. In evaluated cohort there was higher frequency of D-allele ACE1 rs1799752 compared to population. Depending on the availability of criteria for the severity of coronavirus infection, 44 (44%) patients were diagnosed with severe, 56 (56%) with moderate course. The groups did not significantly differ in age, gender, cardiovascular risk factors and comorbid pathology. In the groups with severe and moderate course, the same distribution of genotypes and alleles of AGT rs4762, AGTR2 rs1403543 and ACE1 rs1799752 was revealed. For the I/D alleles of the ACE1 rs1799752 gene, a significant deviation from the papulation was found in both the group of severe and moderate COVID-19. In the group with a severe course of the disease, a higher frequency of the mutant C-allele of the AGTR1 rs5186 gene was detected. In the same group, a deviation in the frequency ratio of A and C of the AGTR1 rs5186 alleles from Hardy-Weinberg Equilibrium was found. When calculating the risk of severe COVID-19 in the presence of the C-allele compared with the A-allele, an odds ratio 2.092 (95% confidence interval 1.066-4.108) was obtained. The data obtained suggest that the genes polymorphisms of the components of renin-angiotensin-aldosterone system, namely D-allele of ACE1 rs1799752 and C-allele of AGTR1 rs5186, may make it possible to identify groups of patients predisposed to the development of more severe COVID-19.

Polymorphism of ADAMTS-13 gene rs28503257 in Iraqipatients with Hypertension

The aim of this study was to investigate the association of polymorphism of ADAMTS-13 gene to the susceptibility of hypertension in patients with hypertension in an Iraqi population. Forty-five hypertensive patients (23 males and 22 females), their age 40-70 years and 35 healthy controls (18 males and 17 females), their age range between 40-70 years. were selected from Wasit Province using a convenient sampling method. Genetic polymorphism of ADAMTS13) rs28503257 A/G was carried out using TaqMan -PCR. In patients and controls, the genotypic and allelic distributions of adisentgrine and metallopeptedase with a thrombospondin type1 motife13(ADAMTS13) rs28503257 A/G of the study populations were consistent with Hardy-Weinberg equilibrium. The genotypes frequecies of ADAMTS-13 rs 28503257 A/G of patients with hypertension manifested non-significant differences when compared with healthy control group AA =40(89%), AG =5(11) in patients vs. 30(86), 5(14) P=0.67 in controls for each genotype respectively. There were no hypertensive patients or controls carrying the genotype GG in the study sample. The A and G allele frequencies in SNP rs28503257 A/G were not significantly different between the two groups (P&gt;0.05). The A allele was the major one in studied groups with a percent of (0.9286) and (0.9444) in control and patients groups respectively. Whereas the A allele was the minor one with a percent of (0.0714) and (0.0556) in these groups respectively. The association analysis revealed that individuals carrying the homozygous AA genotype were assocaited with hypertension OR=1.3333 (CI95% 0.3537 to 5.0259) and P= 0.6709 indicating that a positive association with the disease.However,the individuals with a hetrozygous AG genotype showed negative association with the disease OR= 0.7500 (CI95% 0.1990 to 2.8271) ,P=0.6709. Although no individuals carrying the genotype GG were observed in patients and controls, the odds ratio can be calculated in the presence of other genotypes OR= 0.7802 (CI95% 0.0151 to 40.2986), P= 0. 9019.These results suggest that the A allele may be considered as a risk allele in hypertension whereas the G allele is a protective allele agianst hypertension. The genetic model for ADAMTS-13 in comparison between hypertensive patients and controls .The dominant model indicated that patients of(AG+GG/AA) genotypes decreased the association with hypertension comparing with control with OR=1.333 CI95%0.3537 to 5.025: patients (40/5 and 0.00) in patients vs.(30/5 and 0.00) with OR== 0.7500(CI95%0.1990 to 2.8271) , P =0.6709,P=0.6709.The recessive model revealed that patients carrier the genotype(AA+AG/GG) increased the association with the disease (0.0/40 and 5) in patients compared with controls(0.00/30 and 5) with OR=1.2817(CI95% 0.0248 to 66.199), P=0. 9019.The Over dominant model revealed that patients carrier the genotype (AA+GG/AG) increased the association with the disease (0.040 and 5) in patients compared with controls (0.00/30 and 5) with OR=1.3333(CI95%0.3537 to5.0259),P=0.6709. In coclusion, the polymorphisms ADAMTS-13 rs28503257 variant A/G with are associated with the susceptibility of hypertension.

From landraces to haplotypes, exploiting a genomic and phenomic approach to identify heat tolerant genotypes within durum wheat landraces

Dry and hot climates severely impact wheat yields, necessitating the development of innovative solutions to accelerate the breeding and selection of more adaptable durum wheat genotypes. The aim of this study was to identify new wheat ecotypes that can bridge the gap between commercial varieties and adaptability to ongoing climate change. In this study, advanced genomic and phenomic techniques were combined to characterize a set of durum wheat landraces derived from single seed descent (SSD). This approach enabled the identification of novel variability in the TdHsp26-A1 and -B1 genes. As a result, 38 durum wheat genotypes were analyzed using targeted enrichment PCR, leading to the identification of 17 novel haplotype combinations with SNPs in the TdHsp26 genes. The response of these SSD haplotypes to heat stress was characterized at both the seedling and tillering growth stages. Phenotypic analysis of contrasting genotypes led to the selection of two distinct genotypes: SSD69 and SSD397. During heat stress, SSD69 exhibited altered accumulation of H2O2 and MDA content under both growth conditions, providing new insights into the oxidative response to heat stress. Additionally, this work identifies phenotypic traits that are suitable for detecting differences between variants. The geographic distribution of the different alleles aligned with the spread of durum wheat from its center of origin.

Infection Frequency and Allelic Variants of Toxoplasma gondii in Wildlife from the Panama Canal Zone

Panama has a large number of wild animal species, which could host a highly diverse amount of genetic variants of Toxoplasma gondii (T. gondii). In this context, we highlight the importance of understanding the population structure of T. gondii in Panamanian wildlife and the genetic variants that can be rapidly transferred to domestic environments. This study analyzed the infection frequency and allelic composition of T. gondii in different tissue samples from wild animals. The infection frequency was measured by the PCR technique using the B1 gene as a molecular marker. The results showed a high frequency (65.6%) of infection in tissue samples collected from 221 wild animals. Stratified analyses for bird and mammal samples showed positivity rates of 67.2% and 70.12%, respectively, with no statistically significant differences. Infection frequency was also measured in five types of organs (brain, liver, heart, lung, and skeletal muscle), which showed homogeneous frequencies. The genetic diversity of the T. gondii population contained in the tissues of wild animals was analyzed by the Multilocus Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique, using five genes called SAG1, SAG2, SAG3, GRA6, and Apico. This analysis revealed the presence of alleles of these genes corresponding to T. gondii lineages I, II, and III. Allele III was only identified with the Apico gene in a single reptile individual analyzed. Our findings indicated diverse allelic distribution at the analyzed loci, suggesting that the tissues were probably infected by non-archetypal individuals of T. gondii.

Investigation of genetic polymorphisms in genes encoding growth factors and dental pulp calcification in orthodontic patients

Background and objectivesPulp calcification is associated with many factors and triggers, including individual genetic predisposition and orthodontic forces. This study aimed to investigate whether genetic polymorphisms in epidermal growth factor (EGF), epidermal growth factor receptor (EGFR1), transforming growth factor-beta 1 (TGFβ1), and transforming growth factor-beta receptor 2 (TGFβR2) are associated with a risk of dental pulp calcifications in orthodontic patients. Materials and methodsDigital orthopantomography (OPG) and genomic DNA from 132 patients were analyzed in this cross-sectional study. Pulp calcification was observed in the maxillary and mandibular first molars. Genomic DNA extracted from saliva cells was used to genotype eight genetic polymorphisms using real-time polymerase chain reaction: EGF (rs2237051 and rs4444903), EGFR (rs2227983 and rs763317), TGFβ1 (rs1800469 and rs4803455), and TGFβR2 (rs3087465 and rs764522). The association between pulp calcification and genetic polymorphisms was analyzed using allelic and genotypic distributions, and haplotype frequencies (P < 0.05). ResultsThe prevalence of pulp calcification was 42.4 % in 490 molars. Genotypic analysis and allelic distribution showed no statistically significant association between the evaluated growth factors and molar calcification (P > 0.05). No haplotype combinations showed a statistically significant difference (P > 0.05). ConclusionThe genetic polymorphisms investigated were not associated with dental pulp calcification in orthodontic patients. Further studies should investigate other polymorphisms in genes encoding growth factors.