Bài báo được đăng ở tạp chí :Diagnostics, Q2 thuộc WoS

[3]. Lan Thi Vu, Yen Thi Thu Hoang, Yen Thi Nguyen, Vien Van Nguyen, Hien Thu Nguyen, Thanh Ha Do, Tuan Phan Hoang (2025). . The Indonesian Biomedical Journal, 1794), 343-352.

Bài báo được đăng ở tạp chí Indonesian Biomedical Journal, Q4 thuộc ESCI/WoS :

5.2. Sản phẩm đào tạo

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5.3. Sản phẩm ứng dụng

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01 quy trình xác định đa hình gen CYP2C9, HLA-B và G6PD bệnh nhân điều trị gút bằng NSAID đạt chuẩn SOP.

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INFORMATION ON RESEARCH RESULTS

1. General information

- Project title: Study on polymorphisms of the CYP2C9, HLA-B, and G6PD genes to develop a genetic testing approach supporting the treatment of gout patients.

- Code number: B2023-TNA-03

- Coordinator: Dr. Nguyen Thu Hien

- Implementing institution: Thai Nguyen University.

- Duration: 24 months (From January 2023 to December 2024; Extended until June 2025.)

2. Objectives

2.1. General Objective

To investigate polymorphisms of the CYP2C9, HLA-B, and G6PD genes in order to develop a genetic testing solution to support the treatment of gout patients.

2.2. Specific Objectives

- To identify CYP2C9, HLA-B, and G6PD gene polymorphisms in gout patients treated with NSAIDs.

- To analyze the association between these gene polymorphisms and adverse drug reactions in gout patients treated with NSAIDs.

- To establish a standard operating procedure (SOP) for detecting CYP2C9, HLA-B, and G6PD gene polymorphisms in gout patients receiving NSAID therapy.

3. Creativeness and innovativeness

- This is the first study in Vietnam to simultaneously investigate the polymorphisms of three genes: CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 in gout patients. The A allele of PSORS1C1 rs9263726 was not consistently associated with HLA-B*58:01 and was not a reliable marker for its detection in this study population.

- For the first time in Vietnam, the association between CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 genotypes and gastrointestinal and cardiovascular adverse effects in gout patients treated with a combination of celecoxib and colchicine has been evaluated.

- The relationships between CYP2C9 rs1057910 and HLA-B*58:01 polymorphisms and hematological and biochemical parameters in Vietnamese gout patients have been analyzed for the first time, revealing significant associations between CYP2C9*X/*3 and HDL-C levels and between HLA-B*58:01 and white blood cell count.

- A Sanger sequencing-based procedure for detecting CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 polymorphisms has been successfully established, tailored to the specific nucleotide variations of each gene.

4. Research results

1). The CYP2C9 rs1057910 polymorphism was identified in 139 gout patients. The most common genotype observed was CYP2C9*1/*1, accounting for 92.09% of the study population. The CYP2C9*1/*3 heterozygous genotype represented 7.19%, while the CYP2C9*3/*3 homozygous mutant genotype was rare, appearing in only 0.72% of cases. Among 133 patients genotyped for HLA-B, two genotype groups were observed: HLA-B*X/*58:01 (12.03%) and HLA-B*X/*X (87.97%). The G6PD Viangchan variant was analyzed in 83 gout patients, all of whom carried the wild-type genotype G6PD*1/*1 (100%). The A allele of PSORS1C1 rs9263726 was not consistently associated with HLA-B*58:01 and was not a reliable marker for its detection in this study population.

2). In 83 gout patients treated with celecoxib combined with colchicine, carriers of the CYP2C9*1/*3 genotype had a markedly higher risk of gastrointestinal (abdominal pain, diarrhea) and cardiovascular (hypertension) adverse effects compared with the CYP2C9*1/*1 group, which showed minimal side effects. Carriers of the HLA-B*58:01 allele were also at greater risk of gastrointestinal (especially abdominal pain) and cardiovascular (hypertension) side effects during combined treatment than non-carriers. Most individuals with the G6PD*1/*1 genotype tolerated the combination therapy well, with only a small proportion experiencing mild abdominal pain, diarrhea, or transient hypertension.

3). The results indicated that the CYP2C9 rs1057910 polymorphism had no significant impact on hematological or most biochemical parameters (p > 0.05), except for HDL-C, where the CYP2C9*X/*3 group showed significantly higher HDL-C levels than the CYP2C9*1/*1 group (p = 0.000). Carriers of the HLA-B*58:01 allele exhibited a significantly higher white blood cell count (WBC) than non-carriers (p = 0.018), while other hematological and biochemical indices showed no notable differences. The G6PD rs137852327 polymorphism showed complete homozygosity for the G allele (G6PD*1/*1). Overall, the hematological and biochemical indices of gout patients were within normal ranges, though WBC, Glu, TC, TG, LDL-C, and uric acid levels were elevated, while HDL-C was decreased.

4). The study successfully established a Sanger sequencing-based protocol to identify CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 polymorphisms, based on the nucleotide variations at specific exons of each gene. Specifically, the CYP2C9 rs1057910 (A→C) variant was identified in exon 3; the HLA-B*58:01 allele was recognized through characteristic nucleotide patterns in exons 2 and 3; and the G6PD rs137852327 (G→A) variant was detected in exon 9. The procedure included the following steps: blood collection, DNA extraction, PCR amplification, gel electrophoresis, product purification, sequencing, and sequence analysis using BioEdit software. Each genotype was determined based on Sanger sequencing chromatogram results.

5. Products

5.1. Journal papers

[1]. Hien Thu Nguyen, Yen Thi Thu Hoang, Thanh Ha Do (2024). Personalized medicine in gout treatment. Journal of Science & Technology, Thai Nguyen University, 220(09): 388–398.

[2]. Hien Thu Nguyen, Ha Thi Bui, Yen Thi Thu Hoang, My Ha Hoang, Manh Duc Ngo, Mai Hoang Nguyen, Thuy Thi Thanh Nguyen, Nhuan Tien Ngo, Quang Viet Nguyen (2025). Genotype Frequency of HLA-B*58:01 and Its Association with Paraclinical Characteristics and PSORS1C1 rs9263726 in Gout Patients. Diagnostics, 15(16), 2114.

[3]. Lan Thi Vu, Yen Thi Thu Hoang, Yen Thi Nguyen, Vien Van Nguyen, Hien Thu Nguyen, Thanh Ha Do, Tuan Phan Hoang (2025). CYP2C9 rs1057910 Genotype and Its Association with Paraclinical Characteristics in Gout Patients in the Northeast Region of Vietnam. The Indonesian Biomedical Journal, 17(4), 343–352.

5.2. Education

Two master’s students successfully completed their theses under the project’s research direction:

[1]. Yen Nguyen Thi (2023), Study on the relationship between CYP2C9 gene polymorphism and adverse reactions in gout patients treated with celecoxib, Master’s Thesis in Applied Biology, University of Sciences – Thai Nguyen University.

[2]. Mui Hoang Thi Thu (2024), Study on the characteristics of the PSORS1C1 rs9263726 single nucleotide polymorphism in gout patients treated at Thai Nguyen Central Hospital, Master’s Thesis in Biotechnology, University of Sciences – Thai Nguyen University.

5.3. In terms of application

+ One report on the frequencies of CYP2C9, HLA-B, and G6PD gene polymorphisms in gout patients treated with NSAIDs.

+ One report on the associations between these gene polymorphisms and adverse drug reactions in gout patients treated with NSAIDs.

+ One SOP-standardized protocol for identifying CYP2C9, HLA-B, and G6PD gene polymorphisms in gout patients treated with NSAIDs.

6. Transfer alternatives, application institutions, impacts, and benefits of research results

The identification of genotype frequencies for CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 contributes to enriching the genetic database of the Vietnamese population and holds practical significance in the personalized treatment of gout. The discovery of associations between these genotypes and gastrointestinal or cardiovascular adverse effects in gout patients treated with a combination of celecoxib and colchicine provides important insights for improving drug safety and efficacy based on individual genetic characteristics. In addition, the study revealed significant associations between CYP2C9*X/*3 and HDL-C levels, as well as between HLA-B*58:01 and white blood cell count, clarifying the role of genetic factors in metabolic alterations among gout patients. The Sanger sequencing-based protocol developed for detecting CYP2C9 rs1057910, HLA-B*58:01, and G6PD rs137852327 polymorphisms can serve as a foundation for pharmacogenetic research and screening for adverse drug reaction risks in gout patients in the future.

The research findings and related scientific publications have been utilized as teaching and research materials for undergraduate and graduate students, PhD candidates, and researchers at the University of Medicine and Pharmacy and the University of Sciences – Thai Nguyen University, as well as other universities in Vietnam.

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