Interaction of Thalassemia and Hb Variants in Southeast Asia: Genotype-Phenotype Relationship

Thalassemia and hemoglobinopathies are characterized by globin gene mutations affecting the production of quantitative and structural defects of the globin chain. α-Thalassemia, β-thalassemia, hemoglobin E (Hb E), and hemoglobin Constant Spring (Hb CS) are very common in Southeast Asian countries. Complex interactions of thalassemia and Hb variants are also common and affect the thalassemia diagnosis with several techniques including Hb typing and DNA analysis. A family study (family pedigree) is required in the proband with a complex interaction of several globin gene defects with rare types. Homozygous β-thalassemia, Hb E/β-thalassemia, and Hb Bart’s hydrops fetalis are severe thalassemia and these diseases have been concerned and included in the prevention and control program in several countries. Understanding the genotype-phenotype could help with the proper laboratory tests, genetic counseling, and effective treatment for the patients

A systematic review and meta-analysis of the global prevalence and relationships among Burkholderia pseudomallei sequence types isolated from humans, animals, and the environment

Background and Aim: Burkholderia pseudomallei, a highly pathogenic bacterium responsible for melioidosis, exhibits ecological ubiquity and thrives within soil and water reservoirs, posing significant infection risks to humans and animals through direct contact. The aim of this study was to elucidate the genetic diversity and prevalence patterns of B. pseudomallei sequence types (STs) across a global spectrum and to understand the relationships between strains isolated from different sources. Materials and Methods: We performed a systematic review and meta-analysis in this study. Extensive research was carried out across three comprehensive databases, including PubMed, Scopus, and ScienceDirect with data collected from 1924 to 2023. Results: A total of 40 carefully selected articles contributed 2737 B. pseudomallei isolates attributed to 729 distinct STs and were incorporated into the systematic review. Among these, ST46 emerged as the most prominent, featuring in 35% of the articles and demonstrating a dominant prevalence, particularly within Southeast Asia. Moreover, ST51 consistently appeared across human, animal, and environmental studies. Subsequently, we performed a meta-analysis, focusing on nine specific STs: ST46, ST51, ST54, ST70, ST84, ST109, ST289, ST325, and ST376. Surprisingly, no statistically significant differences in their pooled prevalence proportions were observed across these compartments for ST46, ST70, ST289, ST325, and ST376 (all p > 0.69). Conversely, the remaining STs, including ST51, ST54, ST84, and ST109, displayed notable variations in their prevalence among the three domains (all p < 0.04). Notably, the pooled prevalence of ST51 in animals and environmental samples surpassed that found in human isolates (p < 0.01). Conclusion: To the best of our knowledge, this study is the first systematic review and meta-analysis to investigate the intricate relationships between STs and their sources and contributes significantly to our understanding of B. pseudomallei diversity within the One Health framework

Thalassemia and Hemoglobin E in Southern Thai Blood Donors

Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%), heterozygous α-thalassemia 1 (1.7%), heterozygous β-thalassemia without α-thalassemia (0.9%), heterozygous Hb E without α-thalassemia (5.2%), double heterozygotes for Hb E/α-thalassemia 1 (1.7%), homozygous Hb E without α-thalassemia (0.9%), and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors

Identification of a novel LDLR p.Glu179Met variant in Thai families with familial hypercholesterolemia and response to treatment with PCSK9 inhibitor

Abstract Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated LDL-C levels. In this study, two FH probands and 9 family members from two families from northeastern Thailand were tested for LDLR, APOB, and PCSK9 variants by whole-exome sequencing, PCR-HRM, and Sanger sequencing. In silico analysis of LDLR was performed to analyse its structure‒function relationship. A novel variant of LDLR (c.535_536delinsAT, p.Glu179Met) was detected in proband 1 and proband 2 in homozygous and heterozygous forms, respectively. A total of 6 of 9 family members were heterozygous for LDLR p.Glu179Met variant. Compared with proband 2, proband 1 had higher baseline TC and LDL-C levels and a poorer response to lipid-lowering therapy combined with a PCSK9 inhibitor. Multiple sequence alignment showed that LDLR p.Glu179Met was located in a fully conserved region. Homology modelling demonstrated that LDLR p.Glu179Met variant lost one H-bond and a negative charge. In conclusion, a novel LDLR p.Glu179Met variant was identified for the first time in Thai FH patients. This was also the first report of homozygous FH patient in Thailand. Our findings may expand the knowledge of FH-causing variants in Thai population, which is beneficial for cascade screening, genetic counselling, and FH management to prevent coronary artery disease

ipPCA subpopulation assignment.

<p>The amalgamated worldwide dataset of 1842 individuals was analyzed by ipPCA. The Thai ethno/geographical labels pertaining to datasets 2 and 3 are italicized; all other labels are the same as those shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079522#pone-0079522-g001" target="_blank">Figure 1</a>. Individuals were assigned into 24 genetically distinct subpopulations (SP1 to 24) by ipPCA. 20 Thai individuals that could not be assigned to subpopulations are not shown. The height of each subpopulation bar is proportional to the number of assigned individuals. </p

Ancestry analysis by ADMIXTURE.

<p>The amalgamated worldwide dataset of 1842 individuals was analyzed by the ADMIXTURE program. The number of K ancestral clusters was varied from 2 to 10. Individuals were grouped according to the subpopulation assignments made by ipPCA (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079522#pone-0079522-g002" target="_blank">Figure 2</a>). The ordering of individuals within each subpopulation group is arbitrary.</p

Consensus population Neighbor-Joining unrooted Tree.

<p>An amalgamated worldwide dataset of 1842 individuals genotyped for 41,569 SNPs was analyzed by PHYLIP. The minor allele frequencies for each population were calculated and used as input to produce the dissimilarity matrix using Nei’s approach for unrooted NJ tree. The data were comprised of 850 individuals from 40 populations (dataset no.1; [29]), 618 Thai individuals (dataset no. 2; [30]) and 374 Thai individuals (dataset no. 3; this study). The Thai individuals from datasets no. 2 and 3 were assumed to belong to the same population and then separated into regional subpopulations based on self-reported origins: Thai (C), Thai (NE), Thai (N) and Thai (S). The other population labels are the same as those reported previously in [29], except “Thai” which has been re-labeled as “Thai-Moken”. The consensus tree from 100 bootstrap replicates is shown, and the bootstrap values are indicated on each node of the tree. Southeast and East Asian populations are ringed and the clades separating Thai subpopulations are in red.</p

High-resolution ipPCA assignment of 992 Thai individuals.

<p>992 Thai individuals from datasets no. 2 and 3 were combined and analyzed by ipPCA utilizing 438,503 SNP markers. Four subpopulations (SPA, B, C and D) were resolved by ipPCA, whereas 20 individuals could not be assigned to a subpopulation and are separated as “Outliers”. The proportions of individuals assigned to each subpopulation are shown for each geographical region based on the available information of self-reported origin (North, Northeast, Central, and South). </p