Distribution Of Genotype Frequencies Research Articles

Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.

Effect of PEAR1, PTGS1 gene polymorphisms on the recurrence of aspirin-treated patients with ischemic stroke in the Han population of China: A 4-year follow-up study.

Platelet endothelial aggregation receptor 1 (PEAR1) and prostaglandin endoperoxide synthase 1 (PTGS1) polymorphisms can affect laboratory aspirin resistance. However, the impact of genetic polymorphisms on the recurrence of ischemic stroke (IS) patients treated with aspirin is not fully understood. This study aimed to examine the relationship between gene polymorphisms of PEAR1 and PTGS1 and IS recurrence in patients treated with aspirin. Peripheral blood samples were collected from 174 patients with nonrecurrent IS and 34 with recurrent IS after aspirin treatment. Follow-up was performed on all patients. PEAR1 rs12041331 and PTGS1 rs10306114 polymorphisms were determined using the PCR fluorescence probe method. And the correlations of them with the clinical characteristics were examined by multivariable logistic regression analysis. The distribution frequencies of PEAR1 rs12041331 and PTGS1 rs10306114 genotypes were in Hardy-Weinberg equilibrium, and there was no significant difference in the distribution of PEAR1 rs12041331 polymorphism. Compared to the nonrecurrent group, the AA genotype of the PTGS1 polymorphism was more frequent in the recurrent group (59.77% vs 35.29%, P = .003), and the A allele also showed a higher frequency than the G allele in the recurrent group (P = .001). Multivariable logistic regression analysis showed that smoking (OR = 5.228, 95% CI: 1.938-14.102, P = .001), coronary heart disease (OR = 4.754, 95% CI: 1.498-15.089, P = .008), and the polymorphism at PTGS1(A>G) AA/AG + GG (OR = 2.955, 95% CI: 1.320-6.616, P = .008) were independently associated with IS recurrence in Chinese patients. Our findings suggested that PTGS rs10306114 polymorphisms should receive more attention in the use of aspirin in patients with IS.

Genetic Analysis of TPM1 Gene Polymorphism (rs11071720) in Patients with Non-Syndromic Cleft Lip/Palate in the South Indian Population. A Case Control Study

The aim of this study was to find out if there was an association between TPM1 gene polymorphism (rs11071720) and non-syndromic cleft lip and palate in humans. Twenty five patients with non-syndromic cleft lip and palate (NSCL/P) and twenty five healthy patients as controls were enrolled in the study. Whole blood drawn from the participants was used to obtain genomic DNA. Sequence specific primers were used to amplify the region spanning the polymorphic site of the TPM1 gene using polymerase chain reaction (PCR). The genotype of the subjects was identified employing the RFLP technique. The genotype and allele frequency distributions in the non-syndromic cleft lip and cleft palate patients and control groups were compared using Chi-square test. In the NSCL/P, the genotype in the order from highest to lowest frequency was TC (48%), followed by CC (32%) and TT (20%). Although the genotype frequency of the case and the control groups were found to be in agreement with Hardy Weinberg Equilibrium, the genotype frequencies TC, CC and TT of the polymorphism (rs11071720) among the two groups were not statistically significant which was evident from the p-value 0.8472. No significant association was found between TPM1 gene (rs11071720) polymorphism and NSCL/P.

Vitamin D and it’s Association with FokI VDR Polymorphism in Patients with Asthma-COPD Overlap

Background: Asthma-COPD overlap is a new phenotype in respiratory ailments. It has been shown that this group of patients might possess vitamin D3 deficiency. The association of vitamin D receptor (VDR) gene polymorphism with serum vitamin D status in ACO patients has not been investigated yet. Objective: To assess the association of VDR gene polymorphism (FokI) with serum vitamin D status in patients with Asthma-COPD overlap. Methods: This cross-sectional study was carried out in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University, Dhaka, from January 2018 to July 2018 on 23 (twenty-three) patients (aged ≥40 years) with ACO. For comparison, 24 (twenty-four) apparently healthy age, smoking duration and BMI matched subjects were selected. For all participants single nucleotide polymorphism of VDR gene FokI (rs10735810) was done by DNA extraction, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Vitamin D3 was measured by using automated analyzer: ARCHITECT Plus ci4100. The results were expressed as mean with standard error (mean±SEM) and frequency distribution. The data were statistically analyzed by Graphpad prism (Version 7) using independent sample ‘t’ test, two sample proportion test, Fisher exact test and ANOVA test. In the interpretation of results, ≤0.05 level of probability (p) was accepted as significant. Results: The mean±SEM of serum 25(OH)D were 16.37±0.78 and 18.46±1.01 ng/ml in control and study groups, respectively. The frequency distribution of FokI genotype was 86.95% (FF), 8.69% (Ff), 4.35% (ff) and 91.66% (FF), 4.17% (Ff), 4.17% (ff) in ACO patients and healthy subjects, respectively. When FoKI VDR SNP was analyzed with serum vitamin D status in patients with ACO, statistically no association was seen. Conclusions: FokI VDR SNP is not associated with serum vitamin D status in patients with ACO. J Rang Med Col. March 2024; Vol. 9, No. 1: 22-27

Evaluation of CYP2C19 Genetic Variant and Its Lack of Association with Valproic Acid Plasma Concentrations Among Zhuang and Han Schizophrenia Patients in Guangxi.

To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations. Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 *1, *2, and *3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression. The study identified five CYP2C19 genotypes at the *2 and *3 loci, with the *3/*3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18-60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age. In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.

Potential risk factors for hypospadias and negative correlation with DICER1 (rs3742330) A>G variant in Algerian population: A case-control study.

Hypospadias continues to be a prevalent congenital anomaly affecting the male external genitalia, characterized by an unclear origin and complex treatment approaches. This study aimed to investigate the risk factors associated with hypospadias and explore its genetic link with the DICER1 rs3742330 variant. The study involved two groups: 105 male children with hypospadias and 111 healthy male children as matched controls. Detailed history and physical examinations were conducted for all patients and controls. PCR-restriction fragment length polymorphism was utilized to identify the DICER1 rs3742330 variant, analyzing genotype distribution and allele frequency. Logistic regression analysis estimated the risk factors for hypospadias. The mean age in the hypospadias group was 4.56 ± 2.50 years. The most prevalent type of hypospadias observed was the anterior type in 60 children (57.14%). Intrauterine growth restriction, advanced maternal age, and gestational hypertension were identified as significant risk factors for hypospadias (p = .011, p = .016, and p = .041, respectively). Regarding the genetic study, no significant difference was found in both genotype and allele frequencies of the DICER1 rs3742330 variant between case and control groups. The rs3742330 variant in the DICER1 gene showed no association with hypospadias cases in the Algerian population. However, multivariate logistic regression analysis identified preterm birth, low birth weight, intrauterine growth restriction, advanced maternal age, gestational diabetes, and rural residence as the most significant independent predictors for hypospadias.

АССОЦИАТИВНАЯ РОЛЬ ПОЛИМОРФИЗМА RS121908987 ГЕНА PRKAG2 В РАЗВИТИИ СИНДРОМА WPW

The study of cardiac arrhythmias and conduction is one of the most urgent and important tasks, since these diseases are often the cause of sudden cardiac death. We assumed that the study of the contribution of "predictor genes" of heart rhythm and conduction disorders would expand knowledge about the etiology and pathogenesis of these diseases. Thus, the purpose of our research was to study the contribution of the rs121908987 polymorphism of the PRKAG2 gene to the development of WPW syndrome. Material and methods: 200 patients with VPU syndrome were examined, among them men n=97 [18:32.66;81]; women n=103 [18;47,92;83]. All patients underwent clinical, laboratory, somatometric, instrumental studies, as well as molecular genetic studies DNA isolation was performed by the standard phenol-chloroform method. Genotyping of the PRKAG2 gene was performed by PCR-PDRF analysis (polymerase chain reaction-polymorphism of restriction fragment lengths). Statistical data processing was carried out using the Excel application software package, Statistica for Windows 10.0, IBM SPSS 20.Differences in the frequency distribution of alleles and genotypes of the PRKAG2 gene between the groups were assessed using the χ2 criterion. The relative risk of disease for a specific allele or genotype was calculated as the odds ratio (OR). Results: a statistically significant predominance of the heterozygous GA genotype in patients with VPU syndrome, compared with those in the control group (8 and 2%, respectively; Table 1). There was also a statistically significant predominance of allele A carriers in the group of patients with VPU syndrome by 4%, compared with those in the control group (2%). The risk of developing PRKAG2 genotype GA syndrome, estimated by OSH, was 2.09 times higher (95% CI 1.88–2.32; p <0.001 compared with genotypes GG and AA, and in carriers of the A allele – 2.04 times higher (95% CI 1.90–2.19; p <0.001) compared with allele A (see Table 2). Conclusions: The results of the study confirmed the contribution of polymorphism rs121908987 of the PRKAG2 gene to the development of VPU syndrome.

Effects of MTHFR C677T polymorphism on homocysteine and vitamin D in women with polycystic ovary syndrome

ObjectivesTo evaluate the correlation between serum vitamin D, homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism in women with polycystic ovary syndrome (PCOS).Study designWe retrospectively compared the serum homocysteine and vitamin D levels and the MTHFR C677T polymorphism in 104 PCOS patients and 104 controls. Parameters related to PCOS were statistically analysed. ResultsComparative analysis revealed that women with PCOS had significantly greater serum homocysteine levels (P = 0.002) and lower vitamin D concentrations (P = 0.040) than controls. The distribution frequency of the MTHFR C677T genotype did not significantly differ between the PCOS group and the control group. (P > 0.05). In the PCOS group, the serum level of homocysteine in the TT group was significantly greater than that in the CT (P = 0.003) and CC (P = 0.002) groups and the level of vitamin D in the TT group was significantly less than that in the CC (P < 0.001) and CT (P = 0.172) groups. The results were similar when the PCOS and control groups were divided according to whether they had insulin resistance. Vitamin D levels were significantly negatively correlated with homocysteine levels in all PCOS patients (r = −0.281, P = 0.004), similarly, vitamin D levels were negatively correlated with homocysteine levels in the CC, CT and TT of PCOS patients. According to multivariate analysis, vitamin D concentration was an independent risk factor for hyperhomocysteinaemia (adjusted OR 1.372, 95 % CI: 1.100–1.712). ConclusionsNo significant differences were found in the distributions of MTHFR C677T genotypes between the PCOS and control groups but these genotypes affected the patients’ serum homocysteine and vitamin D concentrations. Women with the TT genotype have significantly lower vitamin D levels and higher homocysteine levels than women with the CC and CT genotypes. However, because of the limitations of this investigation, large-sample, high-quality prospective studies are needed to further verify these results in the future.

The &lt;i&gt;LGALS1&lt;/i&gt; gene polymorphism is not associated with galectin-1 levels in tumor tissue and blood of colon cancer patients

Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene.&#x0D; Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients.&#x0D; Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis.&#x0D; Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05).&#x0D; Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

The potential up-regulation risk of 3′ UTR SNP (rs10787760 G > A) for the VAX1 gene is associated with NSCLP in the northwest Chinese population

AimsTo investigate the association between single nucleotide polymorphisms (SNPs) in 3′UTR region of VAX1, SYT14 and PAX7 genes and the risk of non-syndromic cleft palate (NSCLP) in a northwest Chinese population. Main methodsA case-control study was conducted in 406 normal controls and 399 NSCLP patients. Using iMLDRTM genotyping technology, eight SNPs of three genes ((rs10787760, rs7086344 at VAX1), (rs1010113, rs851114, and rs485874 at PAX7), and (rs61820397, rs4609425, rs12133399 at SYT14)) were genotyped to investigate the differences in alleles and genotype distribution frequencies between NSCLP patients and healthy controls. RNA Folding Form software was used to predict RNA secondary structure and expression vectors were constructed to explore the function of the relevant SNP. The effect of SNP polymorphism of gene transcription and translation was assessed using qPCR and Western blot analysis.Key findings.Among the eight SNPs of three genes, rs10787760 of VAX1 gene was found to be associated with an increased risk of NSCLP (OR = 1.341,CI = 1.004–1.790) and the GA genotype of rs10787760 increased the risk of cleft lip and/or palate (CL/P) about 1.42 times (p < 0.05), and carrying the A allele might increase the risk of NSCL/P in male (OR = 1.356, 95 % CI = 1.010–1.823). But there was no association observed with cleft palate only (CPO). Cell function experiments revealed that the G to A mutation in rs10787760 up-regulated GFP-VAX1 transcriptional level by 2.39 and 3.13 times in two cell lines respectively, and enhance the protein expression of the VAX1 gene further. RNA secondary structure study showed that the rs10787760 (G > A) had two different secondary structures in 3′UTR region. SignificanceThe rs10787760 variant in the 3′UTR region of VAX1 gene is associated with CL/P in northwest Chinese population. We hypothesize that the machanism of it might be caused by the RNA differenct fold in the 3′UTR region caused by the polymorphism of the gene. Level of evidenceOriginal Reports.

Association between rs1799724 of TNF- α gene and early onset preeclampsia in Chinese: A pilot study

ObjectiveTo investigate the association between polymorphisms of TNF- α (rs1799724, rs1800629), VEGF (rs3025039) and VEGFR1 (rs 722503) and early onset preeclampsia (EOPE) in Chinese. MethodsA total of 132 EOPE patients from January 2016 to December 2018 at the Second Hospital of Tianjin Medical University were selected as the EOPE group, and 156 normal pregnant patients as the Control group. In both groups, 5 ml of peripheral venous blood was obtained after admission. The characteristics of genotype and allele distribution at the four SNPs in the study subjects were examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometric genotyping. ResultsThe genotype frequency distribution and allele frequency distribution of rs1799724 were significantly different between the EOPE group and the Control group (P = 0.002，P = 0.003). The T allele was statistically associated with the development of EOPE under a dominant genetic model (P = 0.001). The genotype and allele frequency distributions of rs1800629, rs3025039, and rs 722503 did not differ significantly between the EOPE group and the Control group (P > 0.05). There was no linkage disequilibrium among rs1799724, rs1800629 and rs3025039 loci, the corresponding haploid cannot be formed. ConclusionsThe rs1799724 of TNF- α gene is a genetic susceptibility locus for EOPE and may be a potential predictors of preeclampsia.

Genetic Association of ICAM-1 (rs5498) Gene Polymorphism With Susceptibility to Stage II Grade B Periodontitis: A Case-Control Study in South Indian Population.

In the contemporary perspective, periodontitis is considered a complex issue triggered and perpetuated by bacteriabut strongly influenced by the way the body reacts to bacterial plaque. Recent research has indicated that variations in genes might have an impact on the development of periodontitis. This study was conducted to explore a probable link between the genetic variations in intercellular adhesion molecule-1 (ICAM-1) represented by rs5498 and the occurrence of periodontitis. Methods: A total of 100 participants, 50 with periodontitis and 50 with periodontally healthy or mild gingivitis, were recruited for this study. Whole blood drawn from the participants was used to obtain genomic DNA. The ICAM-1 gene polymorphism (rs5498) was determined using polymerase chain reaction (PCR) amplification and digestion. The ICAM-1 gene's flanking primers were used to amp up the DNA. For statistical analysis, the genotype that was analyzed using the pattern of restriction fragment length polymorphism was recorded. The Chi-square test compared genotype and allele frequency distributions between both groups. The odds ratio with 95% confidence intervals with each individual allele or genotype was used to compute the risk. Statistical significance was established in all tests when the p-value was less than 0.05. There was no discernible difference between the genotype frequencies of patients and controls χ2df (P = 0.6065). The findings demonstrated that no significant difference was present between the two groups for homozygous or heterozygous mutant genotypes (AA vs. AG+GG; P = 0.6854). There was no discernible difference in the detected frequencies of the A allele (58% vs. 61%), G allele (42% vs. 39%), TT (16% vs. 24%), AG (40% vs. 36%), and TT genotypes in the studied groups. According to the results of the current investigation, the ICAM-1 (rs5498) gene polymorphism is not associated with periodontitis in the population investigated.

Matrix Metalloproteinase-7 Promoter Site Single Nucleotide Polymorphism (-181A>G) in Epithelial Ovarian Cancer in the Eastern Indian Population.

Matrix metalloproteinase-7 (MMP7) plays multiple roles in different stages of tumor development. Elevated MMP7 activity has been reported in ovarian cancer. Single nucleotide polymorphism (SNP) of promoter sites of the MMP7 gene has been shown to cause alteration in gene expression, hence resulting in changes in susceptibility to various diseases and tumor development. The current study evaluated the association of epithelial ovarian cancer risk with MMP7 promoter site -181A>G polymorphism in the population of eastern India. The present case-control study included 64 histopathologically confirmed cases of epithelial ovarian cancer and 100 control subjects. The MMP7 -181A/G polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism. The association between genotypes and epithelial ovarian cancer risk was analyzed by odds ratio (OR) with a 95% confidence interval. The frequencies of AA, AG, and GG genotypes in ovarian cancer cases were 37.5%, 46.9%, and 15.6%, respectively, while that of control subjects were 56%, 36%, and 8%, respectively, in the study population. By taking the wild-type AA genotype as a reference, it was found that genotypeGG was associated with a significant risk for epithelial ovarian cancer (OR: 2.92). Frequency distribution of genotypes did not show any significant association with tumor characteristics like the International Federation of Gynecology and Obstetrics (FIGO) stage, histology, lymph node status, and distant metastasis. The present study demonstrated the association of MMP7 promoter site -181 GG genotype and the G allele with increased risk for epithelial ovarian cancer in the eastern Indian population.

Association between Vitamin D Receptor Fokl and Bsml Gene Polymorphism and Diabetes Mellitus in Nepalese Population

Vitamin D being involved in the secretion of insulin is a known fact. Moreover, studies have shown that steroids might be a factor in influencing insulin sensitivity. Vitamin D receptor (VDR), a factor required for genetic regulation involving vitamin D, thus can be regarded as a good candidate for Diabetes Mellitus (DM). Several studies have been conducted on the association between VDR polymorphism and the risk of DM but did not provide clear-cut answers. This study was conducted to search for the involvement of FokI and BsmI polymorphisms of the VDR gene with DM in a Nepalese population. A total of 200 blood samples were collected; 100 from clinically diagnosed DM patients and 100 from healthy controls. DNA was extracted from blood by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, where FokI and BsmI primers as well as restriction enzymes were used. After restriction digestion, SNPs of FokI (T/C) [rs2228570] and BsmI (A/G) [rs1544410] were assayed using agarose gel electrophoresis. As patients and controls were likened for genotype distribution and allelic frequencies, it was found that the frequency of VDR gene BsmI rs1544410 differed significantly (p &lt; 0.05, each) between cases and control whereas A allele was dominant (91%) in healthy controls with Odd ratio (OR) of 0.55, unlike VDR Fokl were not significantly associated between subjects and control. The data obtained from this research suggests that the VDR gene (especially BsmI) is associated with the risk of DM.

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study.

Introduction Oral squamous cell carcinoma (OSCC)is a highly prevalent and most common form of oral malignancy in the Indian population. Toll-like receptors belong to an important family of receptorsthat are involved in the process of pathogen recognition and mounting immune response. The expression of this receptor is dysregulated on the tumor cells as reported across several cancer types. The genetic variants in this gene could have a profound impact on the expression of the Toll-like receptor 4(TLR4)gene. Objective This study aimed to understand theassociation ofTLR4 gene polymorphism (rs4986790) with OSCC. The objective of this study was to compare the allele and genotype frequencies between the two groups,viz., OSCC and normal healthy subjects, recruited in the study. Materials and methods The blood samples were collected from normal healthy subjects (N = 25) and OSCC patients (N = 25). Genomic DNA was isolated from all samples, and genotyping was performed for the TLR4 gene polymorphism (rs4986790) employing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The frequency distribution of genotypes and alleles across the study groups was determined by the Chi-square test. Results The allele frequency for TLR4 gene polymorphism (rs4986790) in the case group was found to be 60% (A allele) and 40% (G allele), respectively. The study population in both groups were found to agree with the Hardy-Weinberg equilibrium (HWE). The genotype frequency did not differ significantly among the two study groups which was evident from the p-value = 0.8285. Conclusion The present study did not report any significant association of the TLR4 polymorphic marker rs4986790 with OSCC. Further investigations into the association of other polymorphic markers in the TLR4 gene, among the larger population of OSCC patients, could provide evidence of their association with OSCC.

Association Between Total Genotype Score and Muscle Injuries in Top-Level Football Players: a Pilot Study

BackgroundRecently, genetic predisposition to injury has become a popular area of research and the association between a few single nucleotide polymorphisms (SNPs) and the susceptibility to develop musculoskeletal injuries has been shown. This pilot study aimed to investigate the combined effect of common gene polymorphisms previously associated with muscle injuries in Italian soccer players.ResultsA total of 64 Italian male top football players (age 23.1 ± 5.5 years; stature 180.2 ± 7.4 cm; weight 73.0 ± 7.9 kg) were genotyped for four gene polymorphisms [ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739), COL5A1 C > T (rs2722) and MCT1 c.1470A > T (rs1049434)].Muscle injuries were gathered for 10 years (2009–2019). Buccal swabs were used to obtain genomic DNA, and the PCR method was used to genotype the samples. The combined influence of the four polymorphisms studied was calculated using a total genotype score (TGS: from 0 to 100 arbitrary units; a.u.). A genotype score (GS) of 2 was assigned to the “protective” genotype for injuries, a GS of 1 was assigned to the heterozygous genotype while a GS of 0 was assigned to the “worst” genotype.The distribution of genotype frequencies in the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and MCT1 c.1470A > T (rs1049434) polymorphisms was different between non-injured and injured football players (p = 0.001; p = 0.016 and p = 0.005, respectively). The incidence of muscle injuries was significantly different among the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and COL5A1 C > T (rs2722) genotype groups, showing a lower incidence of injuries in the “protective” genotype than “worse” genotype (ACE, p < 0.001; ACTN3, p = 0.005) or intermediate genotype (COL5A1, p = 0.029).The mean TGS in non-injured football players (63.7 ± 13.0 a.u.) was different from that of injured football players (42.5 ± 12.5 a.u., p < 0.001). There was a TGS cut-off point (56.2 a.u.) to discriminate non-injured from injured football players. Players with a TGS beyond this cut-off had an odds ratio of 3.5 (95%CI 1.8–6.8; p < 0.001) to suffer an injury when compared with players with lower TGS.ConclusionsThese preliminary data suggest that carrying a high number of "protective" gene variants could influence an individual's susceptibility to developing muscle injuries in football. Adapting the training load parameters to the athletes’ genetic profile represents today the new frontier of the methodology of training.

Interferon Regulatory Factor 5 Gene Polymorphisms and mRNA Expression Levels Are Associated with Neuromyelitis Optica Spectrum Disorder.

Interferon regulatory factor 5 (IRF5) is a critical transcription factor in the toll-like receptor signaling pathway. It is associated with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. However, the relationship between the functional single nucleotide polymorphisms (SNPs) of IRF5 and its mRNA expression level in patients with neuromyelitis optica spectrum disorder remains unclear. The present study aimed to investigate the relationship between polymorphisms and mRNA expression levels of the IRF5 gene with the incidence of neuromyelitis optica spectrum disorder (NMOSD) in northern Chinese Han people. Two loci of the IRF5 gene (rs2004640 and rs2280714) of 164 patients with NMOSD and 269 healthy subjects were genotyped using the multiple SNaPshot technique. The frequencies of alleles, genotypes, and haplotypes were compared. Stratified analysis was performed according to age, sex, AQP4 status, onset age, and Expanded Disability Status Scale (EDSS) score. The IRF5 mRNA levels in peripheral blood mononuclear cells (PBMCs) of 64 NMOSD patients (32 patients in the acute stage and 32 patients in the remission stage) and 35 healthy subjects were detected by real-time PCR. The association of SNP polymorphisms with the mRNA expression level was determined by nonparametric tests. Allele and genotype frequency distributions of rs2004640 showed significant differences between both groups. Compared to healthy controls, the frequency of rs2004640 T allele markedly increased in patients (OR = 1.51, 95% CI = 1.09-2.08, P = 0.005). Minor allele T and GT genotype of rs2004640 that significantly increases the risk of NMOSD were discovered using genetic inheritance models (codominant, dominant, and overdominant) and haplotype analyses. Subsequent haplotype analyses revealed that the major haplotype "T-A" containing the risk alleles (the SNP sequence of the alleles was rs2004640 and rs2280714) had adverse effects on NMOSD. Based on the stratification analysis according to the EDSS score, the GT genotype frequency in the EDSS ≥ 4 group (38.2%) was markedly lower than that in the EDSS < 4 group (61.8%) (OR = 0.32, 95% CI = 0.15-0.68, P = 0.0054), with a significant difference. The IRF5 mRNA expression level was increased in NMOSD patients compared to that in normal subjects. IRF5 gene polymorphisms may be tightly associated with the genesis and progression of NMOSD in northern Chinese Han people. IRF5 mRNA expression was increased in patients with NMOSD and significantly increased in patients with acute phase. Perhaps IRF5 expression levels can be used as a predictor of disease activity in the future.

Hardy-Weinberg Equilibrium Study of Some Morphogenetic Traits in a Nigerian Population

Background: The Hardy-Weinberg (HW) equilibrium studies the distribution of allelic and genotypic frequencies within a population. It provides a mathematical benchmark for a population that is evolving and not evolving. Aim: This study investigated six morphogenetic traits among families in a Nigerian population using the Hardy-Weinberg principle with the aim of evaluating if the population was in HW equilibrium. Methodology: A total of 45 families comprising a father, mother and at least one offspring were conveniently sampled in Ogbe- Ijoh district in Delta State, Nigeria. Earlobe attachment, Hand clasping, Hitchhiker’s thumb, Leg folding, Morton's toe and Widow's peak were studied for their allelic and genotypic frequencies. The Chi-square test was used to analyse the association between these traits and sex, and conformance to the Mendelian inheritance pattern was evaluated with a Mendelian Chi-square. The Hardy-Weinberg equilibrium compared the allelic frequencies of parents with those of offspring. Results: Males had higher frequencies for attached earlobes, Morton’s toe and widow's peak (35.1, 51.9, 49.4%), while the females showed a predominance for hitchhiker's thumb, right hand clasping and leg folding (50,72.4,70.7%). There was no association between the traits and gender (p&gt;0.05). From the Mendelian Chi-square, free earlobe, right-hand clasping, right leg folding, Morton's toe (SBt), the recessive phenotype of hitchhiker's thumb as well as widow's peak were the dominant traits in the studied population (X2 &lt; 3.841 ). The H-W equation revealed a deviation of the offspring’s genotype from those of the parents for earlobe, hand clasping, leg folding, Morton’s toe and widow's peak (1:1:2 [1:1; 4]; 2: 1: 3 [1:1:2]; 3:1:3 [1:1:2]; 5: 1: 4 [6:1:5}; 5:1:4 [7: 1:5]). However, parental and offspring alleles were identical for hitchhiker's thumb (5:1:5 [5:1: 5]). The homozygotes for both parents and offspring outnumbered the heterozygotes for all traits (295: 245; 156: 119). Conclusion: The study showed that only the hitchhiker's thumb was in HW equilibrium, suggesting that evolution may not occur at that locus. KEYWORDS: Hardy-Weinberg equilibrium, Mendel, Traits, Nigeria, Population.

Distribution of the SLC2A9 genotype and its association with the uric acid level in patients with arterial hypertension and atrial fibrillation

Asymptomatic hyperuricemia (HU) is widespread in the population and is one of the main risk factors for cardiovascular diseases. Evidence of numerous studies supports the association between increased uric acid (UA) levels and the risk of arterial hypertension (HTN) and/or atrial fibrillation (AF). One of the causes for an increase in UA levels and a significant risk factor for HU is the polymorphism of the SLC2A9 gene, a highly specific urate transporter in proximal renal tubule cells, encoding the GLUT9 protein.The aim of the study is to investigate the frequency of genotypes and alleles of the SLC2A9 gene rs734553 polymorphic variant and its association with the UA level in patients with HTN and AF, as well as in healthy individuals. 141 patients, including 50 healthy patients (group 1), 68 – with HTN and AF (group 2), 23 – with HTN (group 3) were examined.In the overall group of patients, the frequencies of the SLC2A9 gene rs734553 polymorphism were as follows: AA – 46.1 % (n = 65), AC – 36.2 % (n = 51), CC – 17.7 % (n = 25). According to the genotyping results of patients, in group 1 the AA genotype was 64 % (n = 32), AC – 22 % (n = 11), CC – 14 % (n = 7); in group 2 – 32.4 % (n = 22), 48.5 % (n = 33) and 19.1 % (n = 13); in group 3 47.8 % (n = 11), 30.4 % (n = 7) and 21.7 % (n = 5), respectively. The CC genotype patients (420 [413; 424] μmol/l) and the AC genotype patients (330 [284; 412] μmol/l) had higher uricemia values than those with the AA genotype (310 [281; 341] μmol/l) ( p = 0,003). HU with the AA genotype in group 2 was diagnosed in 2 (2.9 %) patients, with the AC genotype in 12 (17.6 %), and with the CC genotype in 10 (14.7 %) patients; in group 3 – 1 (4.3 %), 1 (4.3 %) and 3 (13 %), respectively. One patient (2 %) with HU in group 1 had the CC genotype.The distribution of genotype and allele frequencies of the SLC2A9 gene rs734553 polymorphic variant and its association with the UA level in patients with HTN and AF, as well as in healthy individuals were established. In patients with HTN and AF, the AC genotype occurred 3 times more often and the CC genotype occurred 2 times more often than in healthy patients. HU occurred significantly more often ( р = 0.003) in the group of patients with HTN and AF and the CC genotype, as well as in patients with the CC genotype.