Genome-wide association and polygenic risk score estimation of type 2 diabetes mellitus in Kinh Vietnamese-A pilot study.

A genome-wide association study (GWAS) is a powerful tool in investigating genetic contribution, which is a crucial factor in the development of complex multifactorial diseases, such as type 2 diabetes mellitus. Type 2 diabetes mellitus is a major healthcare burden in the Western Pacific region; however, there is limited availability of genetic-associated data for type 2 diabetes in Southeast Asia, especially among the Kinh Vietnamese population. This lack of information exacerbates global healthcare disparities. In this study, 997 Kinh Vietnamese individuals (503 with type 2 diabetes and 494 controls) were prospectively recruited and their clinical and paraclinical information was recorded. DNA samples were collected and whole genome genotyping was performed. Standard quality control and genetic imputation using the 1000 Genomes database were executed. A polygenic risk score for type 2 diabetes was generated in different models using East Asian, European, and mix ancestry GWAS summary statistics as training datasets. After quality control and genetic imputation, 107 polymorphisms reached suggestive statistical significance for GWAS (≤5 × 10-6) and rs11079784 was one of the potential markers strongly associated with type 2 diabetes in the studied population. The best polygenic risk score model predicting type 2 diabetes mellitus had AUC = 0.70 (95% confidence interval = 0.62-0.77) based on a mix of ancestral GWAS summary statistics. These data show promising results for genetic association with a polygenic risk score estimation in the Kinh Vietnamese population; the results also highlight the essential role of population diversity in a GWAS of type 2 diabetes mellitus.

Clinical and genetic analysis of Vietnamese patients diagnosed with early-onset Parkinson's disease.

BACKGROUND: Genetic factors play a crucial role in the pathogenesis of Parkinson's disease (PD). However, no comprehensive study has described genetic alterations in Vietnamese patients diagnosed with PD. This study aimed to identify genetic causes and their association with clinical phenotypes in a Vietnamese PD cohort. METHODS: A total of 83 patients with early-onset PD (disease onset before the age of 50) were recruited for genetic analysis using a combination of multiplex ligation-dependent probe amplification and next-generation sequencing for a panel of 20 PD-associated genes. RESULTS: It was found that 37 out of 83 patients carried genetic alterations, with 24 pathogenic/likely pathogenic/risk variants and 25 variants of uncertain significance. The pathogenic/likely pathogenic/risk variants were mostly detected in LRRK2, PRKN, and GBA, while the variants of uncertain significance were identified in 12 different genes that were studied. The most common genetic alteration was LRRK2 c.4883G>C (p.Arg1628Pro), and patients with PD carrying this variant were found to have a distinct phenotype. Participants carrying pathogenic/likely pathogenic/risk variants had a significantly higher rate of a family history of PD. CONCLUSION: These results provide a further understanding of genetic alterations associated with PD in a South-East Asian population.

Association of KCNJ11 and ABCC8 single-nucleotide polymorphisms with type 2 diabetes mellitus in a Kinh Vietnamese population.

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.

Molecular characteristics of young-onset colorectal cancer in Vietnamese patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancer globally. Understanding the genetic characteristics of CRC is essential for appropriate treatment and genetic counseling. METHODS: The genetic profile of CRC tumor tissues was identified using next-generation sequencing of 17 target genes (MLH1, MSH2, MSH6, PMS2, EPCAM, APC, SMAD4, BMPR1A, MUTYH, STK11, PTEN, TP53, ATM, CDH1, CHEK2, POLE, and POLD1) in a cohort of 101 Vietnamese patients diagnosed with young-onset CRC. Corresponding germline genetic alterations of determined somatic mutations were subsequently confirmed from patients' blood samples. RESULTS: Somatic mutations were determined in 96 out of 101 CRC patients. Two-thirds of the tumors harbored more than two mutations, and the most prevalent mutated genes were TP53 and APC. Among confirmed germline mutations, 10 pathogenic mutations and 11 variants of unknown significance were identified. CONCLUSIONS: Given the burden of CRC and the gradually reducing cost of genetic testing, multigene panel screening can benefit young-onset CRC patients as well as their relatives.