Significant Differences In Allele Frequencies Research Articles

Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.

Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear. The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes. The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005). These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.

The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients

PurposeTo investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. Materials/Methods76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. ResultsAmong these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. ConclusionThe study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

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 &lt; 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 &gt; G (rs889022) and IVS10 + 32T &gt; 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 &lt; 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.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

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.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Research on the Correlation Between rs2110385 Polymorphisms of the Visfatin Gene and Nonproliferative Diabetic Retinopathy

Objective: To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy (DR). Methods: 172 Han subjects were selected from Xi’an Shaanxi Province；140 patients with type 2 diabetes mellitus (T2DM) and 32 normal controls (NC) were selected from our hospital. Patients with diabetes were divided into a non-DR group (T2DM) (n = 69) and a nonproliferative diabetic retinopathy Group (DR) (n =71) after dilated fundus photography and fundus fluorescein angiography. rs2110385/Alu Ⅰ genotypes were detected by standardized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the differences in the detection rates of different genotypes in the above populations were compared. Results: 1) The visfatin level in the DR Group was significantly higher than that in the NC and T2DM groups (P &lt; 0.05). 2) The frequency of GG genotype and G allele of rs2110385 in the DR Group were higher than those in the T2DM and NC groups (80.3, 69.6, 50.0, 86.6, 79, 65.6, P &lt; 0.05). 3) There were significant differences in allele frequency and genotype frequency distribution of rs2110385 between the DR Group and the NC group (P &lt; 0.01). Conclusion: Visfatin increased in the nonproliferative diabetic retinopathy group and could be a potential indicator for the clinical prediction of DR. The G allele of the rs2110385 polymorphic site may be related to the risk of DR.

Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms

To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ［91.7%(33/36) vs 59.5%(22/37)］. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1β level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that age（OR =0.917， 95%CI ：0.843-0.999, P =0.047）, thrombosis history (OR =34.148， 95%CI ：2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065， 95%CI ：1.217-212.024， P =0.035), and elevated level of IL-1β (OR =0.929， 95%CI ：0.870-0.992， P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717， 95%CI ：2.690-292.482， P =0.012) and ASXL1 (OR =7.941， 95%CI ：1.045-60.353， P =0.045) were independent risk factors for CCEs in PV. There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1β elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 β elevated levels may be the novel risk factors for CCEs in MPN.

Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children

ABSTRACT Objective To investigate the association between loci rs3761847 and rs10818488 of tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) gene and the susceptibility to IgAV. Methods 100 blood samples of children with IgAV and 100 blood samples of healthy children were collected from the Third Xiangya Hospital of Central South University from June 2017 to June 2019. The target gene fragment was amplified by polymerase chain reaction (PCR), and the single nucleic acid gene polymorphism of the gene loci was detected by PCR sequencing based typing technique. The association between gene polymorphism of each locus and susceptibility to IgAV was analyzed. Results There were significant differences in both genotype (P < .05) and allele frequencies （P < .05) of rs3761847 of TRAF1/C5 gene between the IgAV group and the control group.Besides, the risks of developing IgAV in children with the TT genotype was 0.495 times and in children with the C allele was 1.627 times of that in children with other genotypes and alleles, respectively (P < .05). For IgAV patients, renal involvement risk in children with CC genotype was 5.859 times of that in children with other genotypes (P < .05). There were no significant differences in genotype (P > .05) and allele frequencies (P > .05) of rs10818488 of TRAF1/C5 gene between the IgAV group and the control group. IgAV patients with TT genotype had a 3.2 times higher risk of renal involvement than those with other genotypes (P < .05). Conclusions There is an association between locus rs3761847 of TRAF1/C5 gene single nucleotide polymorphisms and susceptibility to IgAV. The T allele at locus rs3761847 of TRAF1/C5 gene may be a protective factor for IgAV. The C allele at locus rs3761847 and the T allele at locus rs10818488 of TRAF1/C5 gene may be associated with kidney injury in IgAV.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis

BackgroundLong non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility.MethodsA total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls.ResultsNo significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls.ConclusionsOur study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

Comprehensive whole-genome analyses of the UK Biobank reveal significant sex differences in both genotype missingness and allele frequency on the X chromosome.

The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including in the UK Biobank, but the X chromosome was excluded. Our recent report identified multiple regions on the X chromosome with significant sdMAF, using short-read sequencing of other datasets. We performed a whole genome sdMAF analysis, with ~410k white British individuals from the UK Biobank, using array genotyped, imputed or exome sequencing data. We observed marked sdMAF on the X chromosome, particularly at the boundaries between the pseudo-autosomal regions (PAR) and the non-PAR (NPR), as well as throughout the NPR, consistent with our earlier report. A small fraction of autosomal SNPs also showed significant sdMAF. Using the centrally imputed data, which relied mostly on low-coverage whole genome sequence, resulted in 2.1% of NPR SNPs with significant sdMAF. The whole exome sequencing also displays sdMAF on the X chromosome, including some NPR SNPs with heterozygous genotype calls in males. Genotyping, sequencing and imputation of X chromosomal SNPs requires further attention to ensure the integrity for downstream association analysis.

Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option

BackgroundPreeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.ObjectiveThis study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.MethodsIn this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.ResultsOur statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.ConclusionsNo risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

Investigating the role of genetic variation in vgll3 and six6 in the domestication of gilthead seabream (Sparus aurata Linnaeus) and European seabass (Dicentrarchus labrax Linnaeus).

Gene function conservation is crucial in molecular ecology, especially for key traits like growth and maturation in teleost fish. The vgll3 and six6 genes are known to influence age-at-maturity in Atlantic salmon, but their impact on other fish species is poorly understood. Here, we investigated the association of vgll3 and six6 in the domestication of gilthead seabream and European seabass, both undergoing selective breeding for growth-related traits in the Mediterranean. We analysed two different sets of samples using two different genotyping approaches. The first dataset comprised farmed and wild populations from Greece, genotyped for SNPs within the two genes ('gene-level genotyping'). The second dataset examined 300-600 k SNPs located in the chromosomes of the two genes, derived from a meta-analysis of a Pool-Seq experiment involving farmed and wild populations distributed widely across the Mediterranean ('chromosome-level genotyping'). The gene-level analysis revealed a statistically significant allele frequency differences between farmed and wild populations on both genes in each species. This finding was partially supported by the chromosome-level analysis, identifying highly differentiated regions may be involved in the domestication process at varying distances from the candidate genes. Noteworthy genomic features were found, such as a CpG island in gilthead seabream and novel candidate genes in European seabass, warranting further investigation. These findings support a putative role of vgll3 and six6 in the maturation and growth of gilthead seabream and European seabass, emphasizing the need for further research on their conserved function.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia

To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

DNMT1 SNPs (rs2114724 and rs2228611) associated with positive symptoms in Chinese patients with schizophrenia

ObjectiveSchizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia.MethodsThe study was case–control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy–Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed.ResultsThere were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724–rs 2228611 was complete linkage disequilibrium, and rs 1569686–rs 2424908, rs 2424932–rs 1569696 and rs 2424932–rs 2424908 were strongly linkage disequilibrium.ConclusionThe polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection

BackgroundTo examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.MethodsA total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.ResultsTwo SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis.ConclusionsThis study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.

Rare peptide anchors of HLA class I alleles contribute to the COVID-19 disease severity and T cell memory

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Association Between Apolipoprotein C-3 SstⅠ Polymorphism and Serum Lipids in Patients With Gestational Diabetes Mellitus

To investigate the apolipoprotein C-3 (APOC3) gene Sst Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM). A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of APOC3 Sst Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay. The allele frequencies of S1 and S2 of the APOC3 polymorphism at the SstⅠ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of APOC3 Sst Ⅰ polymorphism between the GDM and the control groups ( P>0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all P<0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of APOC3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of APOC3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did ( P<0.05 and P<0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did ( P<0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls. APOC3 Sst Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.

Pharmacogenetic analysis of inter-ethnic variability in the uptake transporter SLCO1B1 gene in Colombian, Mozambican, and Portuguese populations

BackgroundStatin-induced myopathy is reported to be associated with the solute carrier organic anion transporter family member 1B1 gene single nucleotide polymorphism, c.521 T > C. There is no epidemiologic data on this gene polymorphism in several countries. Therefore, this study aimed at assessing the genotype and allele frequencies of the gene variant in three countries.MethodsThis study involved healthy individuals from Colombia, Mozambique, and Portugal. Genomic DNA was isolated from blood samples using the Qiamp DNA Extraction Kit (Qiagen). The isolated DNA was genotyped using novel Polymerase Chain Reaction—Restriction Fragment Length Polymorphism. Microstat and GraphPad QuickCal software were used for the Chi-square test and the evaluation of Hardy–Weinberg equilibrium respectively.ResultsA total of 181 individuals’ blood samples were analyzed. Overall, the TT (74.0%) genotype was the highest and the CC (7.8%) was the lowest. Country wise genotypic frequencies were Colombia 47(70.2%) TT, 12(17.9%) TC and 8(11.9%) CC; Mozambique 47(88.7%) TT, 5(9.4%) TC, and 1(1.9%) CC; and Portugal 40(65.6%) TT, 16(26.2%) TC, and 5(8.2%) CC. The reference (T) allele was highest among Mozambicans (93.4%) compared to Colombians (79.1%) and Portuguese (78.7%). Mozambicans showed statistically significant genotypic and allelic frequency differences compared to Colombians (p < 0.01) and Portuguese (p < 0.01).ConclusionsOverall and country-wise, CC genotype was less frequent and it is relatively high for Colombians and Portuguese populations. This finding may imply statins risk–benefit variability associated with CC genotype among these populations that needs further understanding.