Analysis Of Genetic Polymorphisms Research Articles

Glutathione S -transferase (M1 and T1) and angiotensin-converting enzyme gene polymorphisms and chronic kidney disease in Bangladeshi population

Chronic kidney disease (CKD) is a worldwide public health problem that affects a huge number of individuals and documented as a global public health problem. This study was conducted to uncover the association of gene polymorphism of Glutathione S -transferase M1 (GSTM1, rs366631), Glutathione S -transferase T1 (GSTT1, rs17856199), Angiotensin converting enzyme- Insertion/Deletion (ACE-I/D, rs4646994), and Cytochrome P450 Family 11 Subfamily B Member 2 − 344 T/C (CYP11B2 − 344 T/C, rs1799998) with the risk of development of CKD in Bangladeshi population. Blood samples were drawn from 355 participants (175 CKD patients and 180 healthy controls) by an expert phlebotomist. Different techniques like allele-specific multiplex PCR (Polymerase chain reaction), allele-specific PCR, and PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) were used for the genetic polymorphism analysis. Significant associations were evident for GSTT1 null genotype (OR = 2.45; 95% CI = 1.56–3.82; p < 0.001), combined GSTM1-GSTT1 null genotype (OR = 4.16; 95% CI = 1.99–8.64; p < 0.001) and homozygous mutant variant (DD) of ACE- I/D gene (OR = 4.60; 95% CI = 1.77–12.00; p < 0.01). Homozygous mutant variant (DD) of ACE- I/D polymorphism was found to be more prevalent in the male CKD subjects. It is apparent from our findings that the null genotype of GSTT1, combined GSTM1-GSTT1 null genotype, and homozygous mutant variant (DD) of ACE- I/D could be associated with CKD susceptibility.

Demographic expansion and high level of matrilineal diversity in two populations of East African Baggara cattle.

Western Baggara cattle breed (WBCB) is an East African zebu inhabiting Sudan, well-known as beef-producing cattle. We investigated herein two phenotypically and geographically distinct populations of this breed, namely Nyalawi and Daeinawi, which are renowned for their unique meat production capabilities and adaptation attributes, with the aim to contribute to our understanding of their maternal genetic diversity and demography dynamics. Genetic polymorphism analysis of the full-length D-loop mtDNA region revealed 44 and 35 polymorphic sites defining 28 and 24 distinct haplotypes in the Nyalawi and the Daeinawi, respectively. Observed genetic diversity is high within the population with a low level of genetic differentiation between populations. Approximate Bayesian computation via the calculation of Bayesian skyline plots and neutrality tests support past expansion with a higher maternal effective population size (Ne ) in Nyalawi compared with the Daeinawi population and a population expansion beginning around 4,500YBP and 3,500YBP, respectively, before the arrival of zebu into the continent.

Mathematical modeling of pregnancy loss with normal embryo karyotype in the first trimester

Introduction. The risk of pregnancy loss in the first trimester comprises 12.5-18.7 %. It is timely and relevant to develop methods for predicting miscarriage.Aim: to develop a predictive model for assessing a risk of miscarriage in case of normal embryo karyotype.Materials and Methods. The single-center cohort retrospective comparative study included 52 women with miscarriage at 6-12 weeks of gestation with normal embryo karyotype (main group) and 126 women with physiologically proceeding pregnancies and favorable perinatal outcomes (control group). All patients underwent general clinical and laboratory examination, analysis of genetic polymorphisms (FGBG -455A, F2 G20210A, F5 G1691A, F7 G10976A, F13 G103A, PAI-1 -675 5G/4G, ITGA2 C708T, ITGB3 T176C, MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, NOS3 T-786C, NOS3 C894T), spouse examination.Results. The factors associated with the loss of pregnancy turned out to be presented by a history of infertility, patient adenomyosis, a higher platelet count, as well as abnormal partner spermogram. Significant differences were obtained between the studied groups in the frequency of concurrent polymorphisms PAI-1 -675 5G/4G, MTHFR C677T, MTRR A66G, NOS3 G894T. Based on the identified patterns, a mathematical model has been developed allowing to determine the high risk of pregnancy loss in the first trimester (86.0 % efficiency).Conclusion. A comprehensive assessment of clinical and anamnestic indicators, molecular genetic parameters, spouse-related health indicators, it is possible to determine risk groups of pregnancy loss in case a normal embryo karyotype. Timely prediction provides the basis for optimizing preconception care and conducting timely prevention of miscarriage.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities’ growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 μg/g, with significant differences between the villages (Kruskal–Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0–1.8), high blood pressure (PR: 1.6; CI95%: 1.3–2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3–2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2–2.3), with pregnancy (PR: 1.5; CI95%: 1.0–2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0–3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4–4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Association Association of genetic variant of OXTR (rs53576) and MTNR-1B (rs10830963 and rs1387153) with symptoms of stress in Pakistani women with Gestational Diabetes.

Background: Pregnancy continues to be an event full of risks, complications and adverse outcomes for women despite advanced clinical and diagnostic methods and treatment options available in medicine. Diabetes, as a multifactorial and complex disease, is a possible outcome of a blend of numerous genetic variants of differing scarcities. The exact etiology of gestational diabetes mellitus (GDM) is unclear; however, the interaction of genetic and environmental factors, especially the genetic variants identified as the genetic loci for type 2 diabetes as candidate genes for GDM.&#x0D; Methodology: It will be a case-control study with a genetic analysis of single nucleotide polymorphisms (SNPs) of candidate genes expressed using real-time PCR with sequencing. The study will also evaluate the primer sequence of SNPs.&#x0D; Discussion: We will be able to share the findings after the completion of our research. The results of this study will able helpful in addressing the psycho-physiological needs of women with GDM, which may also be used to devise strategies to benefit the sustainable long-term behavioural change following the affected pregnancy.

Genetic polymorphism and phylogenetic analysis of 15 autosomal STR markers in the Santal indigenous population of Bangladesh

Fifteen autosomal STR markers, namely D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA were typed using AmpFlSTR® Identifiler® Plus PCR amplification systems in 132 unrelated Santal individuals of Bangladesh. Forensic efficiency parameters like, matching probability (MP), power of discrimination (PD), polymorphism information content (PIC), power of exclusion (PE), typical paternity index (TPI), observed heterozygosity (Hobs), and expected heterozygosity (Hexp) were calculated for all the loci. No deviations from Hardy-Weinberg equilibrium were detected for the loci after Bonferroni correction. The combined matching probability (MP), combined power of discrimination (PD) and combined power of exclusion (PE) for the 15 tested STR markers were 8.38 x 10-17, 0.999999998 and 0.0.999993866, respectively. A comparison of the locus wise allele frequencies of autosomal STR data of the Santal population with the published geographically close population data based on Nei’s genetic distance revealed that the Santal population is closely related to Munda population from Jharkhand, India.&#x0D; Bioresearch Commu. 7(2): 1004-1009, 2021 (June)

P621 Lactose intolerance assessed by analysis of genetic polymorphism, breath test and symptoms in patients with inflammatory bowel disease

Abstract Background Many patients with inflammatory bowel disease (IBD) make restriction of dairy products to control their symptoms. We aimed to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission with symptoms suggestive for lactose intolerance, compared to a sex- age- and BMI-matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910CC (genetic wildtype) and the intermediate phenotype LCT-22018AG, LCT-13910CT and we assess the correlation between genotype and H-BT Methods We performed a prospective study enrolling IBD patients in clinical remission: Crohn disease (CD) activity index CDAI&amp;lt;150 for CD and pMayo score≤1 for ulcerative colitis (UC) and controls. All of them underwent clinical evaluation, H-BT and genetic test analysing lactase gene polymorphisms located on chromosome 2. Statistical analysis was performed using chi-square, Student’s t-test and ANOVA. Results A total of 54 IBD patients and 69 matched controls were enrolled. H-BT was positive in 35(64.8%) IBD patients and 43 (62.3%) controls (p=0.3). No significant difference in lactose intolerance rate, assessed by H-BT and symptoms,was found between CD and UC patients (p =0.8). The wild-type genotype was found in 46 (85.2%) IBD patients , CT22018, AG13910 and CT22018/AG13910 polymorphisms were found in 9.3%, 1.8% and 3.7% respectively. While in the control group, the wild-type genotype, CT22018, AG13910 and CT22018/AG13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. The wild type and polymorphisms’ prevalence did not differ between IBD population and control group (85.2%vs 87%, p=0.1) (14.8% vs 13%, p=0.7) [Fig.1] and between CD and UC (p&amp;gt;0.05) [Fig.2]. The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73–16.29, p=0.003) and in the IBD population (OR 7.61, 95%CI 1.36–42.7, p=0.02), even thought not in the control group (OR 4, 95%CI 0.90–17.68, p=0.07) Fig.1 Fig.2 Conclusion The prevalence of lactose intolerance in IBD is high but not dissimilar from that of the general population. The prevalence of the wild-type genotype in patients with IBD does not differ from the general population and it correlates with higher rate of lactose intolerance assessed with H-BT. Despite suggestive symptoms, about 1/3 of IBD patients is not lactose intolerant, not needing elimination diet. These can lead to promote a rationale and balanced dietary management in IBD and thereby preventing the occurrence of calcium phosphate metabolism disorders.

Perspectives of osteoarthritis prevention and therapy personification based on the analysis of comorbid background, genetic polymorphisms and microelement status

Objective: analysis of the osteoarthritis (OA) comorbidity taking into account the microelement status and genetic polymorphisms of the examined patients, determination of the prospects for the OA prevention and therapy.Material and methods. A cross-sectional study of a multiethnic cohort (n=655, mean age 43±14 years, 95% CI 29–70) formed on the basis of the Institute of Microelements database, was carried out. For all participants, the content of the 62 elements of the Element Periodic Table profile in hair was identified and variants of 120 nucleotide polymorphisms associated with various pathologies were definedResults. The study found that 18 of the 27 ICD-10 diagnoses examined were comorbid with OA. Osteoarthritis was comorbid with pathologies with a pronounced component of inflammation (ulcerative colitis, atherosclerosis, unspecified encephalopathy, obesity, diabetes mellitus, essential (primary) hypertension, urine calculus, acute myocardial infarction, cholelithiasis, etc.). The core of OA comorbidity was established, which included following pathologies: chronic cerebral ischemia, diabetes mellitus, thrombophlebitis, atherosclerosis, cholelithiasis. Seven profiles of the most frequent combinations of these diagnoses were identified. The presence of 2 out of 5 of these pathologies was recorded in 92% of patients with OA (n=50) and only in 2% of control patients (n=600), which corresponded to an extreme increase in the risk of OA (OR 56.3, 95% CI 17.4–181.6, p&lt;10–20). Analysis of the 62 elements profile of the Element Periodic Table content in hair showed that reduced levels of silicon, molybdenum, vanadium and calcium are significantly associated with OA. As a result of studying data on 120 nucleotide polymorphisms, OA was significantly associated with the LPL Ser447Stop CC, LPL N291S AA, NOS3 E298D GG, and MTHFR 677 CC genotypes, which regulate lipid metabolism and inflammation.Conclusion. Based on the obtained results the prospects for the use of chondroitin sulfate and glucosamine sulfate in patients with an increased risk of OA development are shown.

Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival.

Background: There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA–microRNA (miRNA) binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC. Methods: We conducted a case–control study of 507 patients with CRC recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′UTR) with susceptibility to CRC and patients’ survival. In addition, genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′UTR of KRAS were selected for analysis using the Haploview and HaploReg software. Results: Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent non-neoplastic large intestinal mucosa. The rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with susceptibility to CRC (adjusted odds ratio (OR): 2.414, 95% CI: 1.385–4.206). Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). Patients having CRC carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio (HR): 4.328, 95% CI: 1.236–15.147). Conclusions: Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for susceptibility to CRC and patients’ survival.

Lactose Intolerance Assessed by Analysis of Genetic Polymorphism, Breath Test and Symptoms in Patients with Inflammatory Bowel Disease.

Many patients with inflammatory bowel disease (IBD) restrict dairy products to control their symptoms. The aim of the study was to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission compared to a sex, age and BMI matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910 CC (wildtype) and the intermediate phenotype LCT-22018 CT and LCT-13910 AG; finally, we assess the correlation between genotype and H-BT. A total of 54 IBD patients and 69 control who underwent clinical evaluation, H-BT and genetic test were enrolled. H-BT was positive in 64.8% IBD patients and 62.3% control (p = 0.3). The wild-type genotype was found in 85.2% IBD patients while CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 9.3%, 1.8% and 3.7%. In the control group, the wild-type genotype, CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. Therefore, the wild-type and polymorphisms’ prevalence did not differ between IBD population and control group (85.2% vs. 87%, p = 0.1) (14.8% vs. 13%, p = 0.7). The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73–16.29, p = 0.003) and in the IBD (OR 7.61, 95%CI 1.36–42.7, p = 0.02). The prevalence of lactose intolerance in IBD patients did not differ from that of control. Despite suggestive symptoms, about 1/3 of IBD patients are not lactose intolerant, thus not needing “a priori” elimination diet. This may encourage a rationale and balanced dietary management in IBD.

IL-13 and FOXO3 genes polymorphisms regulate IgE levels in asthmatic patients.

Immunoglobulin E (IgE) serves a crucial role in the pathogenesis of several allergic disorders, and elevated levels of total serum IgE have been associated with asthma. IgE is responsible for the release of several asthma-associated inflammatory mediators from mast cells, such as histamine and prostaglandins. The aim of the present study was to assess the association of interleukin (IL)-13 single nucleotide polymorphism (SNP) rs20541 and forkhead box O3a (FOXO3a) SNP rs13217795 with IgE levels in asthmatic patients and a healthy control group. Genetic polymorphism analysis of SNPs was performed using PCR/restriction fragment length polymorphism. Total serum IgE levels were measured using an ELISA kit. Genotypes were grouped into three models: Co-dominant, dominant and recessive. Major and minor alleles for IL-13 SNP rs20541 and FOXO3a SNP rs13217795 were C and T, whereas for IL-13, they were G and A, respectively. There was a significant association between the IL-13 rs20541 SNP and the total IgE serum levels, in which pure minor alleles were associated with a significant reduction (~5x lower) in IgE serum levels compared with the major alleles in asthmatic subjects and to a lesser extent in the control subjects. Additionally, the FOXO3a rs13217795 SNP was associated with a significant increase in total IgE levels (~5x higher) in the asthmatic patients compared with the control subjects. In conclusion, the present study confirmed that there was a significant association between the IL-13 SNP rs20541 and asthma, and an association between the FOXO3a SNP rs13217795 with asthma pathogenicity in Jordanian subjects.

Analysis of Genetic Polymorphism and the Identification of the mi-RNA Binding Sites of the Hypoxia Related Genes in Indian Breeds of Cattle

Background: There are certain cattle breeds which are adaptable to the temperate type environmental conditions of high altitude regions of Himalayas. The genome of such cattle have signature of adaptability in the genes related to the hypoxia. Therefore, the current study was undertaken on three hypoxia related genes (EGLN2, EGLN3 and EPAS1) in four breeds of cattle adapted to the diverse agro-climatic conditions of high (Ladakhi and Siri) and low (Hallikar and Kankrej) altitude.Methods: The genotyping of the samples was carried out by using 777 K BovineHD BeadChip (Illumina) at Agri genome Pvt. Ltd (Kerala) and the in-silico analysis of the samples was carried out at ICAR-NBAGR during 2019-2020. The SNPs underlying the genes were evaluated for the gene and genotypic frequencies at nine SNP loci residing in these three candidate genes (EGLN2, EGLN3 and EPAS1). The diversity parameters for these SNPs were assessed by GenAlEx 6.2 software and Minor Allele Frequency (MAF) differences among the breeds were calculated by Duncan’s Multiple Range Test (DMRT) using SAS software. The mi-RNA binding sites in the 3’UTR region of genes were identified by TargetScan software.Result: Higher level of polymorphism was obtained in the Ladakhi and Siri breeds of cattle of high altitude/ cold adapted region than Hallikar and Kankrej of plain and hot arid/ semi-arid region. Several mi-RNA binding sites were obtained in the 3’UTR region of these 3 genes by Target Scan software. The polymorphism obtained in these candidate genes can be utilized in the markers assisted selection of the animals more adapted to the extreme cold and high altitude region for their genetic improvement as well as designing tools for the therapy of the diseases prevalent at high altitude.

Features of the COPD course in patients with different alleles of C79G (rs1072714) of ADRB2 gene

Chronic obstructive pulmonary disease (COPD) is a widely spread disease, that can be prevented and treated. As it was mentioned in the GOLD guidelines, genetic factors have a prominent impact on the development of COPD. A great amount of different genes is involved into the development of COPD. They influence processes of inflammation, fibrosis and regulation of airways reactivity. Polymorphism of ADRB2 gene is of a particular interest as it is associated with the development of COPD and response to beta-2 agonists, which are the main drugs used in the treatment of COPD. The aim of our study was to investigate an impact of the polymorphism of ADRB2 gene on the clinical course of COPD. We collected source data, medical history in all patients in order to assess smoking status and smoking experience, clinical group of COPD according to GOLD classification, total amount of exacerbations, exacerbations treated in in-patient and out-patient conditions, data about use of antibiotics, glucocorticosteroids and methylxanthines. Blood was collected in all patients for the genetic analysis of ADRB2 gene polymorphism. Among COPD patients 65 (65 %) had changes in ADRB2 gene. 26 patients (26 %) had mutation and 39 patients (39 %) had polymorphism of ADRB2 gene, which indicate possible relation of ADRB2 gene with the COPD development. Patients of group 1, C79C allele carriers, had milder COPD course, which presented with the significant difference in the of GOLD D patients in this group (17.14±7.13 %) and group 2, C79G allele carriers, (58.97±8.15 %) and group 3, G79G allele carriers, (34.61±9.59 %). Group 1 patients had lower amount of exacerbations (2.543±0.281) when compared to group 3 (2.963±0.273), and lower amount of hospital admissions (1.031±0.154) when compared to group 2 (1.332±0.167). Group 1 patients also used less antibiotics then other groups. So, ADRB2 gene polymorphism in C79G positions is a prognostic factor of the severity of COPD course. It is associated with the greater amount of exacerbations and hospitalizations and also greater antibiotic use.

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia.

The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR results in a 1–2-month window period, and subsequent phylogenetics and genetic polymorphism analysis of these genomes was performed. Herein, we report, for the first time, genomic evidence of one case of reinfection in Colombia, exhibiting different SARS-CoV-2 lineage classifications between samples (B.1 and B.1.1.269). Furthermore, we report two cases of possible viral persistence, highlighting the importance of deepening our understanding on the evolutionary intra-host traits of this virus throughout different timeframes of disease progression. These results emphasize the relevance of genomic surveillance as a tool for understanding SARS-CoV-2 infection dynamics, and how this may translate effectively to future control and mitigations efforts, such as the national vaccination program.

Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children.

Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.

Genetic diversity analysis in Chinese miniature pigs using swine leukocyte antigen complex microsatellites.

ObjectiveThe swine leukocyte antigen (SLA) gene group, which is closely linked and highly polymorphic, has important biomedical significance in the protection and utilization of germplasm resources. However, genetic polymorphism analyses of SLA microsatellite markers in Chinese miniature pigs are limited.MethodsEighteen pairs of microsatellite primers were used to amplify the SLA regions of seven miniature pig breeds and three wild boar breeds (n = 346) from different regions of China. The indexes of genetic polymorphism, including expected heterozygosity (He), polymorphic information content (PIC), and haplotype, were analyzed. The genetic differentiation coefficient (Fst) and neighbor-joining methods were used for cluster analysis of the breeds.ResultsIn miniature pigs, the SLA I region had the highest numbers of polymorphisms, followed by the SLA II and SLA III regions; the region near the centromere had the lowest number of polymorphisms. Among the seven miniature pig breeds, Diannan small-ear pigs had the highest genetic diversity (PIC value = 0.6396), whereas the genetic diversity of the Hebao pig was the lowest (PIC value = 0.4330). The Fst values in the Mingguang small-ear, Diannan small-ear, and Yunnan wild boars were less than 0.05. According to phylogenetic cluster analysis, the South-China-type miniature pigs clustered into one group, among which Mingguang small-ear pigs clustered with Diannan small-ear pigs. Haplotype analysis revealed that the SLA I, II, and III regions could be constructed into 13, 7, and 11 common haplotypes, respectively.ConclusionThis study validates the high genetic diversity of the Chinese miniature pig. Mingguang small-ear pigs have close kinship with Diannan small-ear pigs, implying that they may have similar genetic backgrounds and originate from the same population. This study also provides a foundation for genetic breeding, genetic resource protection, and classification of Chinese miniature pigs.

Genetic association analysis of ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms with rheumatoid arthritis in a Chinese population

ObjectiveThis study was performed to test whether ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms were associated with RA and further examine the genetic interaction between ATG16L1 and ATG16L2 in RA among a Chinese population. MethodsA total of 594 RA patients and 604 healthy controls were included, and the genetic polymorphisms were genotyped based on HI-SNP technology. ResultsSignificant associations of ATG16L1 rs2241880 polymorphism with RA (T/T versus C/T + C/C, OR = 1.32, 95% CI 1.04–1.67, P = 0.02), cyclic citrullinated peptide (CCP)-positive RA (genotype comparison, P = 5.38 × 10−3; T/T versus C/T + C/C, OR = 1.45, 95% CI 1.12–1.87, P = 4.86 × 10−3) and rheumatoid factor (RF)-positive RA (genotype comparison, P = 0.03; T versus C, OR = 1.23, 95% CI 1.01–1.49, P = 0.04; T/T versus C/T + C/C, OR = 1.44, 95% CI 1.10–1.88, P = 7.62 × 10−3) were found. Significant genetic interaction between ATG16L1 rs2241880 and ATG16L2 rs11235604 was associated RA (P = 0.03), and significant genetic interaction between ATG16L1 rs6758317 and ATG16L2 rs11235604 was associated with RA (P = 7.57 × 10−3), CCP-positive RA (P = 0.01) and RF-positive RA (P = 0.01). Consistently, stratification analysis found that significant associations of RA with ATG16L1 rs2241880, rs6758317 polymorphisms were only detected among individuals carrying C/T genotype of the ATG16L2 rs11235604 polymorphism. ConclusionsOur results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.

A Regulatory Role of Chemokine Receptor CXCR3 in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Emphysema.

Chronic obstructive pulmonary disease (COPD)/pulmonary emphysema is driven by the dysregulated airway inflammation and primarily influenced by the interaction between cigarette smoking (CS) and the individual's susceptibility. The inflammation in COPD involves both innate and adaptive immunity. By binding to its specific ligands, chemokine receptor CXCR3 plays an important role in regulating tissue inflammation and damage. In acute animal model challenged with either CS or pathogens, CXCR3 knockout (KO) attenuated lung inflammation and pathology. However, the role of CXCR3 in CS-induced chronic airway inflammation and pulmonary emphysema remains unknown. In this present study, we investigated the effect of CXCR3 in CS-induced pulmonary emphysema in an animal model, and the association between CXCR3 single nucleotide polymorphisms (SNPs) and COPD susceptibility in human subjects. We found that after chronic exposure to side stream CS (SSCS) for 24 weeks, CXCR3 KO mice demonstrated significant airspace enlargement expressed by mean linear intercept (Lm) compared with the wild-type (WT) mice. Consistently, CXCR3 KO mice had significantly higher BAL fluid macrophages and neutrophils, TNFα, and lung homogenate MMP-9 and MMP-12. Through genetic analysis of CXCR3 polymorphisms in a cohort of COPD patients with Han Chinese ethnicity, one CXCR3 SNP, rs2280964, was found to be genetically related to COPD susceptibility. Furthermore, CXCR3 SNP rs2280964 was significantly associated with the levels of serum MMP-9 in COPD patients. Our data from both animal and human studies revealed a novel role of CXCR3 possibly via influencing MMP9 production in the pathogenesis and progression of CS-associated COPD/pulmonary emphysema.

ISSR primer screening for analysis of genetic diversity among Scutellaria tuvensis (Lamiaceae) populations

Using the Diamond DNA kit, high quality nuclear DNA was isolated from dry leaves of the endemic species Scutellaria tuvensis. The selection of primers for ISSR analysis of genetic polymorphism of natural populations is described. During the experiment, 22 primers were tested, their effectiveness was assessed on a point scale. When assessing the primers, the number of reproducible amplified DNA fragments, the clarity and brightness of the obtained fragments, and only distinctive bands were taken into account. As a result, 10 ISSR markers were selected that are the most informative for assessing the population diversity of the species.

Exploring the potential impact of nutritionally actionable genetic polymorphisms on idiopathic male infertility: a review of current evidence.

Infertility affects about 15% of the world's population. In 40%–50% of infertile couples, a male factor underlies the problem, but in about 50% of these cases, the etiology of male infertility remains unexplained. Some clinical data show that lifestyle interventions may contribute to male reproductive health. Cessation of unhealthy habits is suggested for preserving male fertility; there is growing evidence that most preexisting comorbidities, such as obesity and metabolic syndrome, are highly likely to have an impact on male fertility. The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility. Although these polymorphisms are not directly connected with male infertility, they may have a role in specific conditions associated with it, that is, metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage. Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility, but their results have not been synthesized. We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation, by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.