Polymorphic analysis of CYP2C9 gene in Vietnamese population.

Genetic variations in CYP2C9 are associated to inter-individual variability of drugs metabolism and response. The only report has been done previously mainly focusing on the common variant alleles of CYP2C9 in Vietnamese Kinh subjects. However, little is known about the complete spectrum of this gene polymorphism in different ethnic groups of Vietnam. We sequenced the promoter region and all exons of CYP2C9 in 100 healthy unrelated Vietnamese Kinh subjects. Additionally, common CYP2C9 variants, *2 and *3, were also analyzed by RFLP-PCR in extra 194 Kinh subjects and 279 of other four ethnic groups in Vietnam. The results of these common variants observed from five ethnic groups were compared with other populations in the world. Seven previously reported alleles and two genotypes were determined in Kinh subjects. The percentage of CYP2C9*1 and CYP2C9*3 alleles are 96.5 and 3.5%, respectively. We found one novel non-synonymous variant in exon 7 leading to amino acid change at 363 position from proline to histidine. Functional analysis by SIFT and Polyphen-2 indicated that this mutation is intolerant and probably damaging. Prevalence of CYP2C9*2 observed in Vietnamese population was significantly lower compared with that of other populations in the South and West of Asia as well as in Europe. This study provides information of genetic distribution pattern of CYP2C9 in Vietnamese, which would be useful for optimizing drug therapies in Vietnam.

Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations.

Purpose: Retinoblastoma (Rb) is a rare and unique eye cancer that usually develops in the retinas of children less than 5 years old due to mutations in the RB1 gene. About 40% of affected individuals have the heritable form making genetics testing of the RB1 gene important for disease management. This study aims to identify germline mutations in RB1 in a cohort of patients with Rb from northern Vietnam. Methods: Genomic DNA was extracted from peripheral blood of 34 patients with Rb (nine unilateral and 25 bilateral cases) and their available parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1 gene were screened for mutations with direct PCR sequencing. Multiplex ligation-dependent probe amplification (MLPA) was applied for patients with negative sequencing results. In the mutation-positive patients, their available parental DNA was analyzed to determine the parental origin of the mutation. Results: Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four unilateral and 21 bilateral cases). Of these mutations, 19 were detected, including seven nonsense, six frameshift, four splice-site (one was identified in two siblings), and one missense, with Sanger sequencing. Three novel frameshift mutations were discovered in one unilateral and two bilateral patients. MLPA detected mutations in the RB1 gene in six bilateral cases, of whom five had a whole gene deletion (three familial cases) and one had a partial gene deletion (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed five mutations originated from the fathers and one was inherited from a mother who was mosaic for the mutation. Conclusions: This study provides a data set of germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma. Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.