DNA Alterations in the Upstream Region of Exon 1 of OSBPL10 in Northern Thai Patients with Diffuse Large B-Cell Lymphoma

Document Type : Research Articles

Authors

1 Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

2 Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

3 Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Abstract

Background: Lymphoma is the most common hematologic malignancy in Thailand, with diffuse large B-cell lymphoma (DLBCL) being the predominant subtype. Early prognostic indicators are essential for guiding clinical decisions. Genetic alterations, particularly in regulatory regions, may serve as potential biomarkers. This study investigated sequence alterations upstream of exon 1 of the OSBPL10 gene and their clinical relevance in a Northern Thai DLBCL population. Methods: Eighty-five DLBCL patients residing in Northern Thailand were genotyped to assess sequence alterations in the upstream regulatory region of OSBPL10. Results: Two previously reported single nucleotide polymorphisms (SNPs)—rs76150980 (G>C) and rs62244394 (C>G) and two additional alterations not listed in public SNP databases were identified. The heterozygous GC genotype of rs76150980 and the CG genotype of rs62244394 were significantly associated with a reduced risk of extranodal involvement (OR = 0.229 and 0.196, respectively). While no significant difference in overall survival (OS) was observed, individuals carrying the CG/GG genotypes of rs62244394 had significantly longer progression-free survival (PFS) compared to homozygous CC individuals (median PFS: 39.7 months, 95% CI: 30.4–49.0 vs. 17.3 months, 95% CI: 12.4–22.2; p = 0.031). Additionally, two upstream substitutions—C>T at chr3:31,981,252 and G>T at chr3:31,981,259—showed genotype frequencies of CC (87.1%), CT (3.5%), TT (9.4%) and GG (89.4%), GT (2.4%), TT (8.2%), respectively. At the allele level, the T allele at both positions was associated with increased International Prognostic Index risk (OR = 3.615 and 4.717), while the T allele at position 31,981,259 was associated with lower odds of the aggressive non-GCB subtype (OR = 0.324). No significant OS or PFS differences were observed for these variants. Conclusion: Variations upstream of OSBPL10 were associated with extranodal involvement and selected clinical parameters in DLBCL, highlighting the prognostic potential of regulatory-region SNPs and the importance of population-specific genetic diversity in lymphoma research.

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