Codominant Model Research Articles

Maternal and placental ANRIL polymorphisms and preeclampsia susceptibility.

Aim: The possible effects of maternal and placental ANRIL polymorphisms on preeclampsia were examined. Methods: The maternal blood of 315 preeclamptic and 317 control women and the placentas of 103 preeclamptic and 133 control women were enrolled in the study. ANRIL polymorphisms were genotyped using a PCR-RFLP method. Results: The maternal ANRIL rs1333048C variant showed a relationship with a lower risk of preeclampsia in codominant and dominant models. The maternal ANRIL rs4977574G variant had a relationship with a lower risk of preeclampsia in codominant and recessive models. There was an association between the placental rs1333048C variant and alower risk of preeclampsia in codominant and dominant models. Conclusion: Maternal ANRIL rs1333048C and rs4977574G variants and placental rs1333048 variant showed a relationship with alower risk of preeclampsia.

AIF-1 GENE AS STRONG PROGNOSTIC BIOMARKER FOR ORAL CANCER

Objective: Oral Squamous Cell Carcinoma (OSCC), which is the sixth most prevalent type of cancer across the globe caused by cigarette smoking, smokeless tobacco use, excessive and extreme alcohol use, oral trauma, HPV (Human Papilloma Virus) infection as well as genetic mutations. AIF-1(Allograft Inflammatory Factor) has been identified as an inflammatory response modulator, and its increased expression has been linked to carcinogenesis. Methods: In this study, 200 OSCC patients and 200 matched controls were compared to investigate if there was any association between the AIF-1(Allograft Inflammatory Factor) gene and the risk of cancer of oral cavity in the North Indian population. AIF-1(Allograft Inflammatory Factor) gene polymorphism rs2857595 were detected using TaqMan probe assay. Results: The findings of our study revealed that AA genotype of AIF-1(Allograft Inflammatory Factor) Gene increases the susceptibility of Oral Squamous Cell Carcinoma. The association of AA genotype with Oral Squamous Cell Carcinoma is more in co-dominant model and the combination of both the mutant genotypes (AA+AG) is more significantly associated with Oral Squamous Cell Carcinoma in recessive model. GG genotype of AIF-1 (Allograft Inflammatory Factor) gene comes out with a protective effect against the risk of (OSCC Squamous Cell Carcinoma). To further understand the role of AIF-1(Allograft Inflammatory Factor) polymorphism, we compared the association of genotypes with various clinicopathological characteristics of Oral Squamous Cell Carcinoma patients. And we found that the patients with AA genotype have a significantly higher risk of developing high-grade tumors and more nodal involvement. Conclusion: Thus, rs2857595 locus AA genotype of AIF-1(Allograft Inflammatory Factor) can be considered as important point in the development of accurate preventive approach and a prognostic indicator for oral cancer.

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study - preliminary results.

The development of genetic research over recent decades has enabled the discovery of new genetic markers, such as single nucleotide polymorphisms (SNPs). This, as well as the full sequencing of the dog genome, has enabled genome-wide association studies (GWAS) to be used in the search for genetic causes of canine mammary tumours (CMTs). Genotypic data containing 175,000 SNPs, which had been obtained using the Illumina CanineHD BeadChip microarray technique, were available for analysis in this study. The data concerned 118 bitches, including 36 animals with CMT, representing various breeds and age groups. Statistical analysis was performed in two steps: quality control of genotyping data and genome-wide association analysis based on dominant, recessive, overdominant, codominant, and log-additive models with the single SNP effects. A total of 40 different SNPs significantly associated with CMT appearance were detected. Moreover, twelve SNPs showed statistical significance in more than one model. Of all the significant SNPs, two, namely BICF2G630136001 in the overdominant model and TIGRP2P107898_rs9044787 in the log-additive model, reached the 5-8 significance level. The other SNPs were significant to a 1-5 level. In the group of SNPs indicated as significant in the GWAS analysis, several transpired to be localised within genes that may play an important role in CMT.

Longitudinal effects of FTO gene polymorphism on body composition, cardiorespiratory fitness, physical activity, inflammatory markers, and cardiovascular risk in children and adolescents. "The UP & DOWN study".

The role of polymorphism rs9939609 of the FTO gene has been related with fat mass and cardiovascular risk in adults, but it remains unclear in children and adolescents. Hence, the main aim of this study was to determine the FTO polymorphism effects on body composition, cardiorespiratory fitness (CRF), physical activity (PA), inflammatory markers, and cardiovascular risk both in cross-sectional analysis and after two-years of follow-up in children and adolescents. A total of 2129 participants were included in this study. The rs9939609 polymorphism was genotyped. Body composition measurements, CRF, and moderate-to-vigorous PA (MVPA) were determined at baseline and after two-year of follow-up. Moreover, plasma leptin and adiponectin were also determined as inflammatory markers. Furthermore, an index of cardiovascular disease risk factors (CVDRF-I) was calculated. Codominant (TT vs. TA vs. AA) and dominant (AA+AT vs. TT) models were applied for statistical analysis. The results showed a main effect of the FTO genotype on body composition measures in both first and third year (p < 0.05), with lower adiposity in TT compared with AA or AA+AT group. These differences were maintained after accounting for pubertal maturity, sex, age, VO2 max, and MVPA. Moreover, lower leptin level was observed in TT compared to AA+AT group in the third year. An interaction in Gene*Time*Sex was found in height and neck circumference in dominant model (p = 0.047; p = 0.020, respectively). No differences were found in CRF, MVPA nor CVDRF-I between groups. Hence, homozygous TT allele could be a protective factor against weight gain from early childhood.

ApoE gene polymorphisms and metals and their interactions with cognitive function

ObjectiveTo analyze the relationship between plasma metal elements, ApoE gene polymorphisms and the interaction between the two and impaired cognitive function in elderly population.MethodA stratified sample was drawn according to the age of the study population, and 911 subjects were included. Baseline information and health indicators were obtained, and cognitive function status was assessed by health examination, a general questionnaire and Mini-Mental Status Examination. Plasma metal elements were measured, and SNP typing was performed. Binary logistic regression was used to analyze the factors influencing cognitive function status and the association between the SNP genetic pattern of the ApoE gene and cognitive function.ResultsThe differences in gene frequencies and genotype frequencies of the ApoE rs7412 and rs7259620 genotype frequencies were statistically different between the cognitive impairment group and the control group (P < 0.05). statistically differences were found for the codominant model in rs7412-TT compared with the CC genotype (OR = 3.112 (1.159–8.359), P = 0.024) and rs7259620-AA compared with the GG genotype (OR = 1.588 (1.007–2.504), P = 0.047). Statistically differences were found in the recessive models rs7412-TT compared with (CC + CT) (OR = 2.979 (1.112–7.978), P = 0.030), rs7259620-AA compared with (GG + GA), and rs405509-GG compared with (TT + TG) (OR = 1.548(1.022–2.344), P = 0.039) all of which increased the risk of developing cognitive impairment. The differences in plasma Fe, Cu, and Rb concentrations between the case and control groups were significant (P < 0.05). The regression results showed that the plasma Cd concentrations in the Q1 range was a protective factor for cognitive function compared with Q4 (0.510 (0.291–0.892), P = 0.018). Furthermore, there was a multiplicative interaction between the codominant and recessive models for the Q2 concentrations of Cd and the rs7259620 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (codominant model OR = 3.577 (1.496–8.555), P = 0.004, recessive model OR = 3.505 (1.479–8.307), P = 0.004). There was also a multiplicative interaction between Cd and the recessive model at the rs405509 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (OR = 3.169 (1.400-7.175), P = 0.006).ConclusionThe ApoE rs7412, rs7259620 and rs405509 loci were associated with cognitive impairment in the elderly population, and there was an interaction between plasma metalloid Cd and the rs7259620 and rs405509 loci that increased the risk of cognitive impairment in the elderly population.

Polymorphism of glucocorticoid receptor gene (rs41423247) in functional seizures (psychogenic nonepileptic seizures/attacks).

We investigated the association between the glucocorticoid receptor (GR) gene, also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1), rs41423247 polymorphism, and functional seizures (psychogenic nonepileptic seizures/attacks) in a case-control study. We hypothesized that the tested polymorphism has significant associations with functional seizures (psychogenic nonepileptic seizures/attacks) independent from comorbid depression. Seventy patients with functional seizures (psychogenic nonepileptic seizures/attacks), 70 with major depressive disorder (MDD), and 70 healthy controls (HCs) were studied. Their DNAs were analyzed for NR3C1 rs41423247 polymorphism. Genotype and allele frequencies of rs41423247 were different between the three groups. G allele carriers were more frequent in patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD compared to HCs (p = 0.0001). However no significant difference was observed with respect to allele distributions between functional seizures (psychogenic nonepileptic seizures/attacks) and MDD groups (p = 0.391). CC genotype was less often associated with functional seizures (psychogenic nonepileptic seizures/attacks) versus HC: Codominant model; p = 0.001, OR = 0.11, 95% CI = 0.05-0.24, and -2loglilkelihood = 231.7. In comparison between functional seizures (psychogenic nonepileptic seizures/attacks) group and other (MDD + HC) groups, we observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks) (Codominant model; p = 0.001, OR = 5.63, 95% CI = 2.60-12.40 and -2loglikelihood = 245.99). Patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD were significantly more often G allele carriers in rs41423247 compared with HCs. We observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks). However, we could not exclude the possibility of confounding effects of depression. Future genetic studies of patients with functional seizures (psychogenic nonepileptic seizures/attacks) should include a comparison group with depression in addition to a comparison group of HCs.

Association of Methionine Synthase rs1805087 Polymorphism With Arsenic-Related Skin Pigmentary Changes: A Population-Based Case-Control Study

Objective: Chronic arsenic exposure causes skin lesions including skin cancers, pigmentary changes, and keratosis. Genetic polymorphism in arsenic metabolism may increase susceptibility to the development of arsenic-related skin lesions. This study was performed to determine whether arsenic metabolism-related gene variants are associated with arsenic-related pigmentary changes. Methods: This case–control study involved 189 patients with arsenic-related pigmentary changes and 103 controls. Thirty-eight polymorphisms in 10 genes determined by mass spectrometry assay served as candidate drivers of arsenic-induced pigmentary changes. Urine and plasma arsenic levels were determined by inductively coupled plasma mass spectrometry. Hair arsenic concentrations were measured by nondispersive atomic fluorescence spectrometry. Arsenic metabolites in urine were determined using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Serum folate was measured using a folate radio assay kit. Analysis of variance, nonparametric test, or the chi-square test was selected according to the data distribution. Spearman correlation analysis was used to determine the correlation between two parameters. Logistic regression was used to estimate the effect of single-nucleotide polymorphisms. Results: The arsenic concentrations in urine, plasma, and hair and the urine arsenic species were not significantly different between patients and controls. Logistic regression revealed that among the polymorphisms, the methionine synthase (MTR) rs1805087 polymorphism showed a protective effect against arsenic-related pigmentary changes. In the codominant model, the adjusted odds ratio for age, sex, and ethnicity was 0.41 (95% confidence interval [CI], 0.21–0.80; P = 0.008) for the AG genotype and 0.11 (95% CI, 0.02–0.60; P = 0.012) for the GG genotype. Conclusion: MTR polymorphism showed a protective effect against arsenic-related pigmentary changes in the logistic regression model. The effect of MTR rs1805087 might be independent of arsenic metabolism and one-carbon metabolism. More studies are needed to clarify the biological function of MTR rs1805087 and its relationship with the etiology of arsenic-related pigmentary changes.

Coronary artery disease, its associations with ocular, genetic and blood lipid parameters

Background/objectivesTo investigate the associations between ophthalmic parameters, CYP4F2 (rs2108622) and ABCA1 (rs1883025) polymorphisms and coronary artery disease, considering the accessibility, non-invasive origin of retinal examination and its possible resemblance to coronary arteries.Subjects/methodsOverall 165 participants divided into groups based on the coronary angiography results and clinical status: control group (N = 73), MI group (N = 63), 3VD (three vessel disease) (N = 24). All the participants underwent total ophthalmic examination – optical coherence tomography (OCT) and OCT angiography of the macula region were performed and evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride cholesterol (Tg-C) were tested. A standard manufacturer’s protocol for CYP4F2 (rs2108622) and ABCA1 (rs1883025) was used for genotyping with TaqMan probes.ResultsGCL+ layer was thicker in control group vs. 3VD group (74.00; 62.67–94.67 (median; min.-max.) vs. 71.06; 51.33–78.44, p = 0.037). T allele carriers under ABCA1 rs1883025 dominant model were shown to have ticker retina and smaller foveal avascular zone in superficial capillary plexus and smaller Tg-C concentration. ABCA1 rs1883025 was associated with retinal thickness (OR = 0.575, 95% CI 0.348–0.948, p = 0.030). Univariate logistic regression showed that ABCA1 rs1883025 CT genotype is associated with decreased risk for coronary artery disease development under overdominant genetic model (OR = 0.498, 95% CI 0.254–0.976; p = 0.042) and codominant genetic model (OR = 0.468, 95% CI 0.232–0.945, p = 0.034).ConclusionsResults of this study confirmed that non-invasive methods such as OCT of eye might be used for identification of patients at risk of CAD.

Association of 3p21.31 Locus (CXCR6 and LZTFL1) with COVID-19 Outcomes in Brazilian Hospitalyzed Subjects.

The 3p21.31 locus has been associated with severe COVID-19 prognosis in GWAS studies. Here, we evaluated whether three polymorphisms (LZTFL1 rs10490770, CXCR6 rs2234355 and rs2234358) in the reported locus were associated with the need for mechanical ventilation, hospitalization length and death in 102 COVID-19 hospitalized Brazilian subjects. No genetic association was found with the need for mechanical ventilation and hospitalization length. CXCR6 rs2234355 was associated with mortality under the codominance model, with carriers of the A/A genotype having a greater chance of death than A/G (OR: 10.5; 95% CI: 1.55-70.76). Our results further suggest that the CXCR6 genetic variant contributes to COVID-19 outcomes.

Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer

BackgroundCancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients.MethodsThe SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF–MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0).ResultsStratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death.ConclusionRs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.

Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)-well-studied functional variants involved in one-carbon metabolism-and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49-7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis.

Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.

KLK2 single-nucleotide polymorphism rs198977 is associated with increased susceptibility and hyperleukocytosis in AML.

Introduction: Acute myeloid leukemia (AML) is a heterogeneous myeloid malignancy with abnormal molecular diversity. Tissue kallikrein 2 (KLK2) is a kind of serine protease, and has a close relationship with the occurrence and development of malignant tumors. Single nucleotide polymorphism (SNP) of various genes are associated with susceptibility, treatment and survival of AML. Methods: We investigated the association of KLK2 SNPs rs198977 and rs2664155 with AML. We recruited 284 AML patients and 280 healthy controls from the Han population and genotyping KLK2 SNPs rs198977 and rs2664155 by MassARRAY system. Results: Using clinical data from AML patients and controls, including AML susceptibility, blood count, risk stratification, response to induced chemotherapy and survival, our results showed an increased risk of AML susceptibility with KLK2 rs198977 TT genotype in the recessive model. Regarding white blood cell counts in AML patients, the results showed an increased risk of hyperleukocytosis with the TT genotype of KLK2 rs198977 in a codominant model. Moreover, in the recessive model, AML with KLK2 SNPs rs198977 TT genotype had an increased risk of hyperleukocytosis. No significant correlation was found between KLK2 rs2664155 and AML. Discussion: This study suggests that KLK2 rs198977 may be an important genetic factor in the occurrence of AML and hyperleukocytosis in AML, providing a new perspective for disease progression and new therapeutic targets.

The importance of SOCS1 - 1478 CA/del polymorphism and expression in breast cancer: a case-control study in the north of Iran.

This project aimed to evaluate the relationship between the suppressor of cytokine signaling-1 (SOCS1) - 1478 CA > del genetic variation and breast cancer susceptibility. Moreover, we investigated the SOCS1 mRNA expression level in cancerous tissues. A total of 100 patients with breast cancer and 120 healthy individuals were selected. Genomic DNA was extracted from blood. SOCS1 genotyping and relative gene expression were performed using ARMS-PCR (Amplification-Refractory Mutation System-Polymerase Chain Reaction) and real-time PCR, respectively. In breast cancer patients, the prevalence of genotype frequencies of SOCS1 (- 1478 CA > del) CA/CA, CA/del, and del/del was 52, 31, and 17%, respectively. Among controls, the distribution of CA/CA, CA/del, and del/del was 63, 15, and 22%, respectively. The chi-square test reported that a significant difference was observed in the genotypic distribution of SOCS1 (- 1478 CA > del) polymorphism between cases and controls (χ2 = 8.08, P = 0.01). In addition, the presence of the CA/del genotype was associated with an elevated risk of breast cancer (in the codominant model: OR 2.51; 95% CI 1.27-4.96, P = 0.007 and in the over dominant model: OR 2.54; 95% CI 1.32-4.90, P = 0.005). However, there was no significant difference in allelic distributions between the groups (P > 0.05). There was no significant difference in the breast cancer risk associated with the dominant and recessive genetic models when the reference was CA/CA and CA/CA + CA/del genotype, respectively (P = 0.09 and P = 0.38). Moreover, the expression of SOCS1 decreased in cancerous tissues as compared to the adjacent non-cancerous tissues (P < 0.0001). In conclusion, a functional SOCS1 promoter polymorphism (- 1478 CA > del) may affect breast cancer susceptibility.

GCKR and ADIPOQ gene polymorphisms in women with gestational diabetes mellitus

AimsTo investigate the associations of GCKR and ADIPOQ variants with the risk of gestational diabetes mellitus (GDM) in Chinese women.MethodsGCKR rs1260326, ADIPOQ rs266729, and rs1501299 were selected and genotyped in 519 GDM patients and 498 controls. Candidate SNPs were genotyped using multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods, and the association of these SNPs with GDM was analyzed.ResultsWe found that GCKR rs1260326 was significantly associated with an increased risk of GDM in the allele model, the codominant model (CC vs. TT), the dominant model, the recessive model, and the genotypic model distributions (p = 0.0029, p = 0.0022, p = 0.0402, p = 0.0038, and p = 0.0028, respectively). The rs1260326 polymorphism was shown to be associated with 1 h-OGTT level and gravidity in GDM patients (CC vs. TT: p = 0.0475 and p = 0.0220, respectively). Diastolic blood pressure (DBP) was significantly higher in the GDM patients with the rs266729 GG genotype compared to those with the CC or CG genotype (p = 0.0444 and p = 0.0339, respectively). The DBP of the GDM patients with the rs1501299 GT genotype was lower than that of those with the GG genotype (p = 0.0197). There was a weak linkage disequilibrium value between the GCKR and ADIPOQ SNPs.ConclusionsThe genes GCKR and ADIPOQ may be involved in the pathophysiology of GDM.

MiR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71-24.47; OR 2.30, 95% CI: 1.23-4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

Association between AGTR1 (c.1166 A>C) Polymorphisms and Kidney Injury in Hypertension.

High blood pressure is the main cause of cardiovascular diseases. Kidney damage is one of the most common organ secondary damage to hypertension. The study of hypertension gene polymorphisms is an important means of precision treatment of primary hypertension. The objective of this study was to explore the relationship between AGTR1 (c.1166 A>C) gene polymorphisms and hypertension combined with kidney damage, while exploring the relationship between codominant, dominant and recessive gene model and hypertension with kidney injury and the susceptibility of different genotypes to hypertension with kidney injury. The distribution of AGTR1 polymorphism in the AGTR1 in hypertensive patients (hypertension group, 292 patients) and hypertension with kidney injury patients (44 patients) were detected and compared by PCR-melting curve method. The genotype distribution of hypertension and combined groups met Hardy-Weinberg equilibrium (p > 0.05); the distribution difference between the three genotypes was statistically significant (p < 0.05), the codominant, dominant and recessive distribution frequency of genotypes (p < 0.05), and no difference between A allele and C allele (p > 0.05). Our study identified the relationship of AGTRA (c.1166 A>C) with hypertension combined with renal injury, and compared the susceptibility of different genetic models, which may provide novel targets for precision gene therapy of hypertension. URL: https://www.chictr.org.cn/indexEN.html; Unique identifier: ChiCTR2100051472.

The genotypes A/A and C/C of rs17878703 and rs3175105, respectively in HLA-DRB1 confers risk of COVID-19 severity in Bangladeshi population

BackgroundThe severity and mortality rates of COVID-19 caused by SARS-CoV-2 significantly differ between western countries and Bangladesh. Previous studies had shown that the determinants of COVID-19 severity may stem mostly from host factors such as age, immune-status, host-genetic variations. Among the host-genetic factors, variations in different HLA genes emerged as a potential candidate that may confer susceptibility and severity of SARS-CoV-2 infection. Purpose of the studyIn this study, we hypothesized that genotyping of HLA-DRB1 gene of SARS-CoV-2 infected patients may uncover patient-specific disease severity of COVID-19. Methods and resultsIn this study, participants including COVID-19 patients (n = 68) and controls (n = 22) were enrolled. COVID-19 patients were stratified into three groups: Severe (n = 22), Moderate (n = 20), and Mild (n = 26) based on the clinical parameters approved by WHO. Additionally, interleukin 6 (IL-6) levels measurement further confirmed the clinical stratification. To evaluate the landscape of the polymorphism within the HLA-DRB1 gene, whole-exome sequencing (WES) of 29 individuals (patients: n = 22 and controls: n = 7) by the Next Generation Sequencing (NGS) was conducted. Analysis of the WES data revealed 13 annotated non-synonymous variants (8 multi-allelic and 5 bi-allelic) on exon 2 of HLA-DRB1. To further validate these SNPs, Sanger sequencing of 61 individuals comprising of control subjects and COVID-19 patients were done.The genotypes A/A and C/C of rs17878703 and rs3175105 were found to be significantly associated with the risk of COVID-19 by codominant, dominant and recessive genetic models. These two bi-allelic SNPs were in strong disequilibrium (D′ = 0.998, p < 2 × 10−16). A rare haplotype (CACAA) comprising of the alleles of the bi-allelic SNPs (rs17885482, rs17884945, rs3175105, rs9269951 and rs17878703) was found to be significantly associated with COVID-19 severity. ConclusionThe genotypes A/A and C/C of the rs17878703 and rs3175105 within the HLA-DRB1 gene may confer risk to COVID-19 severity. Thus, further study in a larger cohort is needed to comprehensively assess the role of these SNPs in HLA-DRB1 gene with respect to severity of COVID-19 in the Bangladeshi population.

Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case–control study

BackgroundDuring pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM.MethodsThis was a case–control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM.ResultsOnly the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53–3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61–3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600.ConclusionsSNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.

CD33 polymorphisms and Parkinson’s disease Parkinson’s disease in northern Chinese Han population: A case-control study

ObjectiveParkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33’s role as a critical immunoregulatory receptor in neuroinflammatory responses. MethodsThe present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). ResultsAlleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people. ConclusionThis study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD.