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Steven Truong,1,* Nam Quang Tran,2,3,* Phat Tung Ma,2,3 Chi Khanh Hoang,3 Bao Hoang Le,3 Thang Dinh,3 Luong Tran,3 Thang Viet Tran,2,3 Linh Hoang Gia Le,4 Hoang Anh Vu,4 Thao Phuong Mai,5 Minh Duc Do4 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; 2Department of Endocrinology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Department of Endocrinology, University Medical Center, Ho Chi Minh City, Vietnam; 4Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 5Department of Physiology-Pathophysiology-Immunology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam*These authors contributed equally to this workCorrespondence: Minh Duc DoCenter for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang, District 5, Ho Chi Minh City, 700000, Vietnam, Tel +84 932999989, Email ducminh@ump.edu.vnPurpose: Genetic factors play an important role in the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). However, few genetic association studies related to these disorders have been performed with Vietnamese subjects. In this study, the potential associations of ADIPOQ single nucleotide polymorphisms (SNPs) with T2DM and MetS in a Kinh Vietnamese population were investigated.Patients and Methods: A study with 768 subjects was conducted to examine the associations of four ADIPOQ SNPs (rs266729, rs1501299, rs3774261, and rs822393) primarily with T2DM and secondarily with MetS. The TaqMan SNP genotyping assay was used to determine genotypes from subjects’ DNA samples.Results: After statistical adjustment for age, sex, and body mass index, the ADIPOQ SNP rs266729 was found to be associated with increased risk of T2DM under multiple inheritance models: codominant (OR = 2.30, 95% CI = 1.16– 4.58), recessive (OR = 2.17, 95% CI = 1.11– 4.26), and log-additive (OR = 1.32, 95% CI = 1.02– 1.70). However, rs1501299, rs3774261, and rs822393 were not associated with risk for T2DM. Additionally, rs266729, rs3774261, and rs822393 were statistically associated with MetS, while rs1501299 was not. Haplotype analysis showed a strong linkage disequilibrium between the SNP pairs rs266729/rs822393 and rs1501299/rs3774261, and the haplotype rs266729(G)/rs822393(T) was not statistically associated with MetS.Conclusion: The results show that rs266729 is a lead candidate SNP associated with increased risk of developing T2DM and MetS in a Kinh Vietnamese population, while rs3774261 is associated with MetS only. Further functional characterization is needed to uncover the mechanism underlying the potential genotype–phenotype associations.Keywords: genetic association, Kinh Vietnamese, metabolic syndrome, type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a genetically influenced disease, but few studies have been performed to investigate the genetic basis of T2DM in Vietnamese subjects. Thus, the potential associations of KCNJ11 and ABCC8 single nucleotide polymorphisms (SNPs) with T2DM were investigated in a Kinh Vietnamese population. A cross-sectional study consisting of 404 subjects including 202 T2DM cases and 202 non-T2DM controls was designed to examine the potential associations of 4 KCNJ11 and ABCC8 SNPs (rs5219, rs2285676, rs1799859, and rs757110) with T2DM. Genotypes were identified based on restriction fragment length polymorphism and tetra-primer amplification refractory mutation system polymerase chain reaction. After statistically adjusting for age, sex, and BMI, rs5219 was found to be associated with an increased risk of T2DM under 2 inheritance models: codominant (OR = 2.15, 95% confidence intervals [CI] = 1.09-4.22) and recessive (OR = 2.08, 95%CI = 1.09-3.94). On the other hand, rs2285676, rs1799859, and rs757110 were not associated with an increased risk of T2DM. Haplotype analysis elucidated a strong linkage disequilibrium between the 3 SNPs, rs5219, rs2285676, and rs757110. The haplotype rs5219(A)/rs2285676(T)/rs757110(G) was associated with an increased risk of T2DM (OR = 1.42, 95%CI = 1.01-1.99). The results show that rs5219 is a lead candidate SNP associated with an increased risk of developing T2DM in the Kinh Vietnamese population. Further functional characterization is needed to uncover the mechanism underlying the potential genotype-phenotype associations.

Background: The prevalence of diabetes mellitus in Vietnam is relatively low compared to other Asian countries, but it is accelerating with the economic and cultural transition. This study aimed to estimate the current prevalence and clinical profile of undiagnosed diabetes mellitus in a tertiary hospital in the south of Vietnam. Methods: A cross-sectional investigation was conducted to recruit 1, 250 participants, who were at least 18 year-old and randomly sampled from Cho Ray Hospital, Ho Chi Minh City, Vietnam. Fasting plasma glucose concentration and HbA1c were measured for each individual. The American Diabetes Association criteria were used to diagnose diabetes. Demographic data and other clinical characteristics of diabetes were also documented, including age, sex, residence, educational status, weight, height, waist and hip circumferences, blood pressure, familial history of diabetes, and lipid profile. Results: The prevalence of undiagnosed diabetes mellitus was 7.5% in the population studied. Age, waist circumference, waist-hip ratio, body mass index, and hypertension, as well as dyslipidaemia were well-correlated with the diabetes rate. Conclusion: The prevalence of undiagnosed diabetes mellitus is increasing far more than expected. Newly diagnosed diabetic patients usually presented with multiple comorbidities, including overweight/ obesity, hypertension, and dyslipidaemia.

Introduction: Germline mutations in predisposing genes have been found in 30-40% of pheochromocytoma/paraganglioma patients. Screening for inherited genetic mutations provide clinicians with mutation-positive patient management strategies in addition to identifying family members at risk of disease. However, genetic testing for pheochromocytoma has not been performed widely in Vietnam. Methods: Seven patients diagnosed with pheochromocytoma in Vietnam underwent germline genetic testing in known pheochromocytoma-associated genes by direct sequencing. When a germline mutation was identified the first-degree relatives were counseled and offered genetic testing for the inherited mutation. Results: Mutations were found in five of seven cases and all mutations were in RET proto-oncogene codon 634 indicating a high risk of developing aggressive medullary thyroid cancer and in some cases leading to prophylactic thyroidectomy as recommended. Conclusions: Genetic testing plays an essential role in the clinical management of pheochromocytoma patients. Genetic results have significantly changed the clinical approach in these patients and identified ‘at risk’ family members.

Genetic factors play an important role in the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). However, few genetic association studies related to these disorders have been performed with Vietnamese subjects. In this study, the potential associations ofA study with 768 subjects was conducted to examine the associations of fourAfter statistical adjustment for age, sex, and body mass index, theThe results show that rs266729 is a lead candidate SNP associated with increased risk of developing T2DM and MetS in a Kinh Vietnamese population, while rs3774261 is associated with MetS only. Further functional characterization is needed to uncover the mechanism underlying the potential genotype-phenotype associations.

Truong S,Tran NQ,Ma PT, et al. Diabetes Metab Syndr Obes. 2022;15:307–319. The authors have advised that the funding statement on page 316 is incorrect. The text “This work was supported by the MIT UROP Program’s Peter J. Eloranta Research Fellowship and the National Foundation for Science & Technology Development (NAFOSTED), grant number 108.01-2019.319. We thank Christine Mendonca and the Joslin Diabetes Center DRC Core for their assistance in genotyping samples” should read “This research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 108.01-2019.319 and the MIT UROP Program’s Peter J. Eloranta Research Fellowship. We thank Christine Mendonca and the Joslin Diabetes Center DRC Core for their assistance in genotyping samples”. Read the original article

Introduction Genetic mutations of PROC and PROS1 are well-known risk factors for deep venous thrombosis (DVT) in the Asian population. However, the genetic profile of Vietnamese patients with DVT remains elusive. This study aimed to investigate the spectrum of genetic mutations of these two genes in Vietnamese patients diagnosed with idiopathic DVT. Materials and methods A total of 50 Vietnamese patients diagnosed with idiopathic DVT were recruited in this study. The entire coding regions of the protein C and protein S genes were amplified and directly sequenced to determine genetic alterations. Results Four and six genetic mutations were detected in protein C and protein S genes, respectively, in 24 Vietnamese DVT patients. PROC c.565C > T (p.R189W) was the most common mutation found in 13 out of 50 patients, while the mutations of PROS1 comprised three missense and three nonsense variants which diffuse along the gene. Conclusions This study shows that mutations of protein C and protein S genes are prevalent in Vietnamese patients diagnosed with idiopathic DVT, and PROC c.565C > T (p.R189W) was the most common genetic alteration.

Prion diseases are fatal neurodegenerative disorders linked to the deposition of the abnormal prion protein isoform called PrPSc or prion. The key molecular events triggering the diseases are the conformational changes from the normal cellular α-helical prion protein PrPC to the pathological β-sheet enriched PrPSc. Therefore, understanding the mechanism and factors underlying the conversion process is essential to find possible diagnostic tools and treatments. Copper has long been known to correlate with neurodegenerative dysfunctions; PrPC is a copper binding protein via histidine residues in the highly conserved octapeptide repeats (OR) and the non-OR region located in the disordered N-terminal tail of the protein. The role of copper in facilitating protein aggregation and disease progression remains elusive. This study describes the impact of histidine residues on prion replication. By analyzing mouse PrP constructs that carry artificial mutations at histidines in the OR and non-OR, we provide cell evidence for the critical role of the non-OR copper binding site at histidine 95 in prion conversion. We also contribute to better understanding of the mechanisms and primary sites for prion conversion and replication. Our findings establish a platform for further studies aimed at elucidating the role of the H95 mutant in de novo prion diseases when expressed in transgenic mice.