Analysis Of Genetic Polymorphisms Research Articles

Genetic Polymorphism Analysis of 24 Y-STRs in a Han Chinese Population in Luzhou, Southwest China.

Han is the largest of China's 56 ethnic groups and the most populous ethnic group in the world. The Luzhou region is located in southwest China, at the junction of three provinces. The unique historical factors contribute to the genetic polymorphism information. Short tandem repeats (STRs) are highly polymorphic, but the polymorphism of the Y chromosomal STRs (Y-STRs) loci in the Luzhou region is still unclear. It is of great significance to provide Y-STRs genetic data for the Han population from the Luzhou areas of southwest China. A total of 910 unrelated male individuals of the Han population from the Luzhou area were recruited, and 24 Y-STRs were analyzed. The population structure and phylogenetic relationships were compared with those of another 11 related Han populations. A total of 893 different haplotypes were achieved from 910 samples, of which 877 (98.21%) haplotypes were unique. Haplotype diversity and discrimination were 0.999956 and 0.981319, respectively. The lowest genetic diversity of DYS437 is 0.4321, and the highest genetic diversity of DYS385a/b is 0.9642. Pair-to-pair genetic distance and relative probability values indicate that Luzhou Han people are close to Sichuan Han people, Guangdong Han people, and Hunan Han people, which is consistent with geographical distribution, historical influence, and economic development. The 24 Y-STR markers of the southwest Luzhou Han population were highly polymorphic, which provided us with genetic polymorphism information and enriched the population genetic database. Therefore, it is of great value to our forensic applications and population genetics research.

Genetic Polymorphism and Relationship Analyses of Standard Poodle and Bichon Frise Groups Based on 19 Short Tandem Repeat Loci

Abstract Context: As the increasing number of pet canines, the identification of canine has attracted much attentions in the forensic field, however, the genetic diversities of pet canines still remained unknown. Aims: To explore genetic polymorphisms of 19 short tandem repeat (STR) loci and genetic relationships between the two studied canine groups and reference group. Subjects and Methods: In the present study, genetic polymorphisms of 19 STR loci and a sex-linked zinc finger locus were analyzed in a total of 594 canines in Standard Poodle and Bichon Frise groups from China. Results: A total of 166, 159 alleles were observed in the Standard Poodle, Bichon Frise groups with the corresponding allelic frequencies ranging from 0.0030–0.6108 to 0.0012–0.6148, respectively. The combined discrimination power and probability of exclusion of 19 STR loci in Standard Poodle and Bichon Frise groups were 0.9999999999999497, 0.999962884; and 0.99999999999999995, 0.999965955, respectively. Furthermore, the genetic distances between the two canine groups and Labrador retriever group were calculated, and the results indicated that Standard Poodle and Bichon Frise groups showed a closer genetic relationship, while the two canine groups had distant genetic relationships with Labrador retriever group. The result of population genetic structure revealed that genetic component distributions in the three canine groups were different. The predicted accuracies of the constructed random forest prediction model for three validation sets (25% individuals randomly selected from three populations with 808 individuals) were higher than 0.9, especially for the individuals in validation set from the Bichon Frise group is 1. Conclusions: The 19 STR loci could be used for individual identification, canine breed identification and paternity testing in the two canine groups.

Analysis of genetic polymorphism in genes encoding cathelicidins from Vietnam indigenous yellow cattle breeds

Cathelicidins include antimicrobial peptides (AMPs) and are involved in the innate immune defense against infections in mammals. Polymorphisms in the DNA sequence of cathelicidin genes could be relevant to inherited variations of host innate immunity, adaptation, and pathogen resistance. This study aims to investigate the sequence polymorphism of cathelicidin genes including CATHL2 and CATHL4 from local indigenous yellow cattle breeds of Vietnam. Genomic DNA samples were extracted from 52 individuals collected from different cattle populations in Vietnam including Ha Giang, Thanh Hoa, Nghe An and Phu Yen. The CATHL2 and CATHL4 genes were amplified by PCR, following sequencing for identification of the single nucleotide polymorphisms (SNPs) and/or insertion-deletion (indel) DNA sequence variations. The copy number variations (CNVs) of the CATHL4 gene were determined by cloning, single strand conformation polymorphism (SSCP) and real-time PCR. The comparative analysis results showed that there are 13 SNPs detected in all sequences of CATHL2 gene including 9 SNPs in intron 2 and intron 3, and 4 missense substitutions in exon 1, 2, and 3. These SNPs do not affect the predicted tertiary structure of Bac5 encoded by this gene. For CATHL4, the results revealed 15 SNPs, 3 indels and 1 repeat variation as motif (TG)n(G)n/(AC)n(C)n. Among these variations, the deletion 46delC in exon 1 of CATHL4 was detected in a sample of the Ha Giang breed causing a truncated polypeptide as predicted. The average copy number of CATHL4 of Vietnam indigenous cattle breeds using GADPH as a reference gene showed in range from 2.53 to 2.89 copies.

Prognosis of the risk progression of post-inflammatory pneumofibrosis in children with chronic nonspecific lung diseases

Introduction. Pneumofibrosis (PF) is a morphological outcome of acute and chronic lung diseases, the progression of which leads to organ deficiency.Aim. Development of a prognostic algorithm for assessing the risk of progression of post-inflammatory PF in children with chronic nonspecific lung diseases (CNSLD).Materials and methods. The examination of 52 children with CNSLD with focal post-inflammatory PF was conducted, of which 26 children with progressive PF and 26 children with non-progressive PF. The children were selected according to the “case-control” scheme. The patients had a dynamic clinical and laboratory examination with multispiral computed tomography of the lungs. Determination of the “zero” genotypes of the detoxification genes GSTM1, GSTT1 was carried out by means of polymerase chain reaction. The odds ratio indicator was used to assess the relative risk.Results. Based on the analysis of medico-social, clinical characteristics and genetic polymorphism, an individual prognostic algorithm for the risk of progression of post-inflammatory PF in children with CNSLD was developed. The algorithm includes the calculation of the total score (TS) of 7 medical and social indicators (living in an urban area; the presence of passive smoking; the duration of a pulmonological history of 4-9 years; the presence of congenital lung malformation; the number of acute respiratory infections (ARI) 4 or more times/year; the duration of ARI 11 days or more; taking antibiotics for more than 3 once/year) and the presence of deletions in the detoxification genes GSTM1 and GSTT1. With a value of TS 6.97 or more, a high risk of progression of PF is predicted, with TS 3.47-6.96 points, a moderate risk of progression of PF is diagnosed, with TS 3.46 or less points, a minimal risk of progression of PF.Conclusion. The proposed algorithm allows predicting the risk of progression of post-inflammatory PF in children with CNSLD at the stage of early diagnosis and will prevent the spread of the process in the lungs with the help of preventive measures and preventive therapy, which will increase the duration and improve the quality of life of the patient.

Pathological Features and Genetic Polymorphism Analysis of Tomato Spotted Wilt Virus in Infected Tomato Fruit.

An in-house tomato inbred line, YNAU335, was planted in a greenhouse in spring from 2014 to 2017, and showed immunity to tomato spotted wilt virus (TSWV). YNAU335 was infected with TSWV in the spring from 2018 to 2020, and disease was observed on the leaves, sepals, and fruits. In 2021 and 2022, YNAU335 was planted in spring in the same greenhouse, which was suspected of being infected with TSWV, and visible disease symptoms were observed on the fruits. Transmission electron microscopy, deep sequencing of small RNAs, and molecular mutation diagnosis were used to analyze the pathological features and genetic polymorphism of TSWV infecting tomato fruit. Typical TSWV virions were observed in the infected fruits, but not leaves from YNAU335 grown between 2021 and 2022, and cross-infection was very rarely observed. The number of mitochondria and chloroplasts increased, but the damage to the mitochondria was greater than that seen in the chloroplasts. Small RNA deep sequencing revealed the presence of multiple viral species in TSWV-infected and non-infected tomato samples grown between 2014-2022. Many virus species, including TSWV, which accounted for the largest proportion, were detected in the TSWV-infected tomato leaves and fruit. However, a variety of viruses other than TSWV were also detected in the non-infected tissues. The amino acids of TSWV nucleocapsid proteins (NPs) and movement proteins (MPs) from diseased fruits of YNAU335 picked in 2021-2022 were found to be very diverse. Compared with previously identified NPs and MPs from TSWV isolates, those found in this study could be divided into three types: non-resistance-breaking, resistance-breaking, and other isolates. The number of positive clones and a comparison with previously identified amino acid mutations suggested that mutation F at AA118 of the MP (GenBank OL310707) is likely the key to breaking the resistance to TSWV, and this mutation developed only in the infected fruit of YNAU335 grown in 2021 and 2022.

Correlation study of SNP of glycogen degradation metabolism related genes and glycogen content in Haliotis discus hannai

Glycogen is an essential nutritional component of the Pacific abalone (Haliotis discus hannai), and its content is a crucial factor in selecting and breeding high-quality abalone. Glycogen catabolism is facilitated by two key enzymes: glycogen debranching enzyme (GDE) and glycogen phosphorylase (GP). This study aimed to explore the relationship between GDE and GP gene polymorphisms and glycogen content in abalone. To this end, four and two SNP loci located in the exonic regions of these two genes, respectively, were screened and identified in 264 abalone using direct sequencing. The results of genetic polymorphism and correlation analysis revealed a negative correlation between the expression of GDE and GP and glycogen content. Moreover, the study found that the GA haplotype of GDE gene SNP1/3 was significantly associated with high glycogen content, while the TT genotype of GP gene SNP2 was significantly associated with low glycogen content. These results provide molecular markers that could be utilized for selecting and breeding glycogen traits in abalone, indicating the potential influence of GDE and GP polymorphisms on glycogen content.

Forensic genetic analysis of single-nucleotide polymorphisms and microhaplotypes in Koreans through next-generation sequencing using precision ID identity panel.

Forensic DNA analysis has seen remarkable advancements with the advent of Next Generation Sequencing (NGS). In particular, NGS analysis of single nucleotide polymorphisms (SNPs) offers significant advantages in the analysis of challenging samples compared to conventional STR analysis. This study aimed to investigate the SNPs of the Precision ID Identity Panel, a commercially available NGS panel for personal identification, by generating genetic profiles of 298 Koreans and comparing them with other global populations. A total of 124 SNPs, including 90 autosomal and 34 Y-SNPs, were analyzed using the Precision ID Identity Panel, and forensic parameters, microhaplotypes, and population differences were investigated. The NGS data were successfully obtained from 298 Koreans. The analysis of forensic parameters exhibited a low combined match probability of 1.532 × 10- 34, which is comparable to that obtained from commonly used STR analysis. Additionally, the microhaplotype analysis revealed that the use of 16 microhaplotypes provided higher discriminatory power compared to single target SNPs. Furthermore, the adoption of microhaplotype data resulted in an increase of over 20% in expected heterozygosity at five loci. Inter-population analysis showed a close genetic relationship between Koreans and individuals from China and Myanmar in East and Southeast Asia, which are geographically adjacent to Korea. The results of this study show that the Precision ID Identity panel can be a useful alternative where traditional STR typing is not feasible. Also, the data from our study will be useful as a reference for Koreans in forensic investigations and the prosecution of criminal justice.

Genetic Polymorphism and Population Genetic Structure Analysis of 21 Autosomal STR Loci for a Han-Chinese Population from Luzhou of Southwest China.

The Han nationality is an ancient and populous people, and different places in China may have their distinct group relationships. Luzhou area, as a crossroads of several provinces in Southwest China, lacks autosomal short tandem repeat (STR) research and population genetics research. In this study, 21 autosomal STR loci were evaluated in 1959 Han-Chinese individuals from Luzhou area. There was no substantial linkage disequilibrium (LD) among the 21 autosomal STR markers, and all markers were in Hardy-Weinberg equilibrium (HWE). The total discrimination power (TDP) and cumulative probability of exclusion (CPE) of the 21 autosomal STR loci were calculated to be 1-9.8505 × 10-16 and 1-1.9406 × 10-9, respectively. There were 333 alleles for 21 STRs with allelic frequencies ranging from 0.00026 to 0.51302, and the number of alleles ranged from 7 in locus TPOX to 29 in locus Penta E. According to the results of population comparison and population differentiation, historical influences, geographical distribution, cultural integration, and economic development may have an impact on the Luzhou Han population and other Chinese populations. These 21 STR loci were found to enrich autosomal STR information in forensic databases and provide highly informative polymorphisms for our forensic practice in China, including personal identification and parentage testing.

EZH2 Expression and Survival for ER+/tamoxifen Treated Breast Cancer Patients with rs2302427 C>G: A Novel Prognostic and Risk Predictive Biomarker

Overexpression of the EZH2 gene silences several genes involved in DNA repair, cell-cell adhesion, and tumor suppressor genes, resulting in the development of several types of cancers. In the present study, a genetic polymorphism analysis was performed by selecting three SNPs (rs.2302427C>G, rs.3757441C>T, and rs.6950683T>C) of the EZH2 gene based on our previous in silico studies. A total of 250 breast cancer patients and 250 healthy individuals were recruited for the study. Patients with pre-operative breast cancer with different clinical-pathological variables and age-matched healthy women were recruited for the EZH2 gene expression analysis. The genetic polymorphism analysis revealed two SNPs (rs.2302427C>G and rs.6950683T>C) of the three studied SNPs of the EZH2 gene have a protective role in all three genetic models. The haplotype analysis predicted that two haplotypes ACGT and ACGC were significantly associated with a lower risk of breast cancer. Three significant findings of the SNP rs.2302427C>G (Asp193His) i.e., protective role against breast cancer, survival advantage in ER+/tamoxifen treated breast cancer patients, and decreased expression due to the presence of mutant GG genotype, suggests considering it as an important prognostic biomarker for a good survival outcome of breast cancer patients treated with ER+/tamoxifen. Compared with other studies, the other SNP rs.3757441T>C was observed to have a protective effect in breast cancer biology but plays an antagonistic role in colorectal cancer (CRC) biology. To our knowledge, this is the first detailed study on computationally validated EZH2 SNPs in breast cancer.

Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels.

As a disease with high mortality and prevalence rates worldwide, colorectal cancer (CRC) has been thoroughly investigated. Mucins are involved in the induction of CRC and the regulation of intestinal homeostasis but a member of the mucin gene family MUC4 has a controversial role in CRC. MUC4 has been associated with either decreased susceptibility to or a worse prognosis of CRC. In our study, the multifunctional aspects of MUC4 were elucidated by genetic polymorphism analysis in a case-control study of 420 controls and 464 CRC patients. MUC4 rs1104760 A>G polymorphism had a protective effect on CRC risk (AG, AOR = 0.537; GG, AOR = 0.297; dominant model, AOR = 0.493; recessive model, AOR = 0.382) and MUC4 rs2688513 A>G was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). In addition, MUC4 rs1104760 A>G showed a high probability of being a potential biomarker for CRC patients with low-density lipoprotein cholesterol (LDL-C) in the risk range while showing a significant synergistic effect with the LDL-C level. This is the first study to indicate a significant association between MUC4 genetic polymorphisms and CRC prevalence, suggesting a functional genetic variant with the LDL-C level, for CRC prevention.

Association between inducible nitric oxide synthase-954-G>C and Ex16+14-C>T gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis

Background Psoriasis is a prevalent disorder of primarily skin and joint affection with a well-known genetic background and a sophisticated pathogenesis. The inducible nitric oxide synthase (iNOS) gene polymorphisms are unexplored areas of research when it comes to psoriasis. Objectives The aim of the study was to investigate the probable link between iNOS gene polymorphisms (-954 G/C and Ex 16+14C/T) and susceptibility to psoriasis and psoriatic arthritis (PsA). Patients and methods We included three groups of participants: 100 participants each of psoriasis, PsA and healthy controls. Genetic polymorphism analysis was performed utilizing the PCR with the restriction fragment length polymorphism method. Results Genetic analysis of iNOS polymorphism at Ex 16+14C/T revealed significantly increased CT genotype frequency and significantly lower CC genotype frequency in psoriasis (P=0.0011, 0.003, respectively) and PsA patients (P=0.001, P<0.0001, respectively) in comparison to controls. Genetic analysis of iNOS polymorphism at −954 G/C revealed insignificant difference in genotype distribution between psoriasis patients and controls, whereas significantly increased GC genotype frequency (P=0.038) and significantly decreased GG genotype frequency (P=0.038) were detected in PsA patients versus healthy controls. Conclusions iNOS polymorphism at Ex 16+14C/T, particularly the CT genotype, is associated with psoriasis in Egyptians, whereas PsA is associated with polymorphism at Ex 16+14 and −954G/C.

Identification of Genetic Polymorphisms of PI, PIII, and Exon 53 in the Acetyl-CoA Carboxylase-α (ACACα) Gene and Their Association with Milk Composition Traits of Najdi Sheep.

Recently, increasing attention has been paid to sheep milk products, which are high in saturated fatty acids (SFA), and the extent of their impact on human health. This study aimed to identify SNPs for PI, PIII, and Exon 53 in the ACACα gene and their association with the MC and FA profiles in Najdi sheep milk. A total of 76 multiparous Najdi ewes were used, and they were maintained using the same feeding system. Milk and blood samples were collected during the first lactation. A genetic polymorphism analysis identified 20 SNPs: 4 SNPs on PI, 6 SNPs on PIII, and 10 SNPs on Exon 53. In PI, the SNP g.4412G > A was associated (p < 0.05) with palmitic acid (C16:0), palmitoleic acid (16:1 n-7) and linoleic acid (LA), while SNP g.4485C > G was associated with CLA and vaccenic acid (VA) (p < 0.05). Furthermore, in PIII, two SNPs (g.1168A > G and g.1331G > T) were associated with milk protein (p < 0.05), while the SNP g.6860G > C in Exon 53 was associated with milk fat (p < 0.05). SNPs in the Najdi breed have been shown to be strongly related to milk fat and EFA contents. This could support a genetic selection program and the control of milk traits in the Najdi breed of high-quality dairy sheep.

Establishment of PCR assays and genetic polymorphism analysis of genes encoding Clostridium perfringens β2 toxin from different sources

Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β2 toxin (cpb2) and atypical-cpb2 (aty-cpb2), analyze the epidemiological characteristics and genetic polymorphism of the cpb2 of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb2 of 188 Clostridium perfringens strains were examined by PCR; the cpb2 sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb2-library based on 110 strains carrying the cpb2 were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb2 (con-cpb2) and aty-cpb2. Results: The specificity of PCR assay for the cpb2 and aty-cpb2 was verified. The PCR results for cpb2 amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb2, 94 types A strains carried aty-cpb2, 6 types A strains carried con-cpb2, and 7 types F strains carried aty-cpb2. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb2 toxin was developed, and the previous PCR method for detecting aty-cpb2 was improved. aty-cpb2 is the primary gene encoding of β2 toxin. There is a significant nucleotide sequence variance between the various cpb2 genotypes.

Selenium as a Factor Moderating Depression and Obesity in Middle-Aged Women

The aim of this study was to evaluate the effect of serum selenium on PPAR-γ and the selected proinflammatory cytokines (IL-1β, IL-6, TNF-α) in relation to depressive symptoms and obesity in middle-aged women. The research procedure was as follows: a survey was performed using the authors' questionnaire and the BDI, anthropometric measurements, and the analysis of blood for the levels of selenium, cytokines, and genetic analysis of the PPAR-γ polymorphism (n = 443). It was found that the BMI increased along with the concentration of IL-6. No moderating effect of selenium was observed, although the cut-off values for "p" were established for IL-β*Se (p = 0.068) and IL-6*Se (p = 0.068), so there was a potential association with these two markers. At high selenium levels, the effect of higher IL-β levels on a decrease in BMI was stronger, as was the effect of an increase in IL-6 levels on an increase in BMI. No effect of selenium on PPAR-γ was found in relation to depressive symptoms and obesity. Higher selenium levels may have a beneficial effect on BMI even at high IL-β concentrations, however, at high IL-6 concentrations, this effect was not observed. Selenium levels had no impact on depressive symptoms.

Genetic Diversity in Natural Populations of Rhodiola Species of Different Adaptation Strategies.

Representatives of the Crassulaceae family's genus Rhodiola are succulents, making them distinctive in a changing environment. One of the most significant tools for analyzing plant resources, including numerous genetic processes in wild populations, is the analysis of molecular genetic polymorphism. This work aimed to look at the polymorphisms of allelic variations of the superoxide dismutase (SOD) and auxin response factor (ARF) gene families, as well as the genetic diversity of five Rhodiola species, using the retrotransposons-based fingerprinting approach. The multi-locus exon-primed intron-crossing (EPIC-PCR) profiling approach was used to examine allelic variations in the SOD and ARF gene families. We implemented the inter-primer binding site (iPBS) PCR amplification technique for genome profiling, which demonstrated a significant level of polymorphism in the Rhodiola samples studied. Natural populations of Rhodiola species have a great capacity for adaptation to unfavorable environmental influences. The genetic variety of wild populations of Rhodiola species leads to their improved tolerance of opposing environmental circumstances and species evolutionary divergence based on the diversity of reproductive systems.

The Analysis of Genetic Polymorphism on Mitochondrial Hypervariable Region III in Thai Population.

Mitochondrial DNA (mtDNA) analysis is a genetic marker for human identification, especially matrilineal inheritance. Hypervariable regions (HVR) I and II of mtDNA have been currently performed for human identification worldwide. Further examination of HVRIII has been conducted with the aim of enhancing the power of discrimination. The aim of this research is to provide informative data on the polymorphisms of HVRIII in the Thai population in order to establish a national database for human identification. Thai people who were unrelated through the maternal lineage were recruited for blood collections. The mtDNA was extracted by Chelex extraction, amplified by polymerase chain reaction, and analyzed using Sequencing Analysis Software. The most common mutation in HVRIII was base substitution, followed by deletion and insertion. We discovered 40 unique haplotypes, with haplotype 489C being the most frequent. The haplotype diversity, power of discrimination, and random match probability were 0.8014, 0.7987, and 0.2013, respectively. Five-CA repeats were the most frequently observed in nucleotide positions 514-523. Our database can be employed as supplementary markers in addition to nuclear deoxyribonucleic acid (DNA) markers in forensic investigations. Moreover, the data could potentially enhance genetic identification and anthropological genetics research in Thailand.

Genotypic and morphological diversity of trematodes Leucochloridium paradoxum.

The sporocysts of the trematode Leucochloridium paradoxum parasitise land snails Succinea putris. The sporocysts form broodsacs whose tegument contains green and brown pigments. The colouration changes during maturation. The pattern and colour of the broodsacs may vary in different individuals and sometimes even in one sporocyst. We studied the broodsacs of 253 sporocysts of L. paradoxum collected in the European part of Russia and Belarus, and identified four main colouration types. An analysis of genetic polymorphism by a fragment (757 bp) of the mitochondrial cox1 gene revealed 22 haplotypes. Using the nucleotide sequences of the cox1 gene fragment of L. paradoxum from Japan and Europe available in GenBank, we constructed haplotype networks. A total of 27 haplotypes were identified. The haplotype diversity of L. paradoxum by this gene was rather low, on the average 0.8320. A low genotypic diversity by the mitochondrial marker is consistent with rDNA conservativeness of Leucochloridium spp. noted previously. The most broadly represented haplotypes, Hap_1 and Нap_3, were described in both sporocysts and adults of L. paradoxum. We suggest that the mobility of birds, which are the definitive hosts of L. paradoxum, provides the necessary conditions for the genotypic diversity of its sporocysts parasitising different populations of snails Succinea putris.

The rs3825807 Polymorphism of ADAMTS7 as a Potential Genetic Marker for Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus.

A disintegrin and metalloprotease with thrombospondin motif 7 (ADAMTS-7) was reported to play a role in the migration of vascular smooth muscle cells and neointimal formation. The object of the study was to investigate the association between the rs3825807 polymorphism of ADAMTS7 and myocardial infarction among patients with type 2 diabetes mellitus in a Slovenian cohort. 1590 Slovenian patients with type 2 diabetes mellitus were enrolled in this retrospective cross-sectional case-control study. In total, 463 had a history of recent myocardial infarction, and 1127 of the subjects in the control group had no clinical signs of coronary artery disease. Genetic analysis of an rs3825807 polymorphism of ADAMTS7 was performed with logistic regression. Patients with the AA genotype had a higher prevalence of myocardial infarction than those in the control group in recessive [odds ratio (OR) 1.647; confidence interval (CI) 1.120-2.407; p = 0.011] and co-dominant (OR 2.153; CI 1.215-3.968; p = 0.011) genetic models. We found a statistically significant association between rs3825807 and myocardial infarction in a cohort of Slovenian patients with type 2 diabetes mellitus. We report that the AA genotype might be a genetic risk factor for myocardial infarction.

Clinical efficacy and safety of individualized pembrolizumab administration based on pharmacokinetic in advanced non-small cell lung cancer: A prospective exploratory clinical trial

IntroductionPembrolizumab is recommended with a fixed dose of 200 mg 3-weekly. We performed this study to explore the clinical efficacy and safety of pharmacokinetic (PK)-guided pembrolizumab administration in advanced non-small cell lung cancer (NSCLC). MethodsIn this prospective exploratory study, we enrolled advanced NSCLC patients in Sun Yat-Sen University Cancer Center. Eligible patients received pembrolizumab 200 mg 3-weekly with or without chemotherapy for four cycles, then for patients without progressive disease (PD), pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (Css) of pembrolizumab until PD. We set the effective concentration (Ce) at 15 μg/ml and new dose-intervals (T) was calculated according to Css of pembrolizumab using following equation: Css × 21D = Ce (15 μg/ml) × T. Primary endpoint was the progression-free survival (PFS), secondary endpoints were objective response rate (ORR) and safety. Besides, advanced NSCLC patients received pembrolizumab 200 mg 3-weekly and more than four cycles in our center were defined as the history-controlled cohort. Patients with Css of pembrolizumab underwent genetic polymorphism analysis of variable number of tandem repeats (VNTR) region in neonatal Fc receptor (FcRn). The study was registered at ClinicalTrials.gov, NCT05226728. ResultsA total 33 patients received pembrolizumab in new adjusted dose-intervals. The Css of pembrolizumab ranged from 11.01 to 61.21 μg/ml, 30 patients need prolonged intervals (22-80d) and 3 shortened intervals (15–20 d). In PK-guided cohort, the median PFS was 15.1 months and ORR 57.6 %, whereas in history-controlled cohort was 7.7 months and ORR 48.2 %. The immune-related adverse events were 15.2 % and 17.9 % between two cohort. The VNTR3/VNTR3 genotype of FcRn had significantly higher Css of pembrolizumab than VNTR2/VNTR3 (p = 0.005). ConclusionsPK-guided pembrolizumab administration showed promising clinical efficacy and manageable toxicity. Meanwhile less frequent dosing of pembrolizumab by PK-guided could reduce financial toxicity potentially. This provided an alternative rational therapeutic strategy of pembrolizumab in advanced NSCLC.

Analysis of MTNR1A Genetic Polymorphisms and Their Association with the Reproductive Performance Parameters in Two Mediterranean Sheep Breeds.

Sheep farming plays an important economic role, and it contributes to the livelihoods of many rural poor in several regions worldwide and particularly in Tunisia. Therefore, the steady improvement of ewes' reproductive performance is a pressing need. The MTNR1A gene has been identified as an important candidate gene that plays a key role in sheep reproduction and its sexual inactivity. It is involved in the control of photoperiod-induced seasonality mediated by melatonin secretion. The aim of this study was to identify SNPs in the MTNR1A gene in two Tunisian breeds, Barbarine (B) and Queue Fine de l'Ouest (QFO). DNA extracted from the blood of 77 adult ewes was sequenced. Selected ewes were exposed to adult fertile rams. A total of 26 SNPs were detected; 15 SNPs in the promoter region and 11 SNPs in the exon II were observed in both (B) and (QFO) breeds. The SNP rs602330706 in exon II is a novel SNP detected for the first time only in the (B) breed. The SNPs rs430181568 and rs40738822721 (SNP18 and SNP20 in our study, respectively) were totally linked in this study and can be considered a single marker. DTL was associated with SNP18 and SNP20 in (B) ewes (p < 0.05); however, no significant difference was detected between the three genotypes (G/G, G/A, and A/A) at these two SNPs. Fertility rate and litter size parameters were not affected by SNP18 and SNP20. There was an association between these two polymorphisms and (B) lambs' birth weights (p < 0.05). Furthermore, the ewes with the A/A genotype gave birth to lambs with a higher weight compared to the other two genotypes for this breed (p < 0.05). There was not an association between SNP 18 and SNP20 and (QFO) ewes' reproductive parameters. These results might be considered in future sheep selection programs for reproductive genetic improvement.