The KIF1B (rs17401966) Single Nucleotide Polymorphism is not Associated with the Development of HBV-related Hepatocellular Carcinoma in Thai Patients

Abstract

Hepatitis B virus (HBV) infection can become chronic and if left untreated can progress to hepatocellular carcinoma (HCC).Thailand is endemic for HBV and HCC is one of the top five cancers, causing deaths among Thai HBV-infected males. A single nucleotide polymorphism (SNP) at the KIF1B gene locus, rs17401966, has been shown to be strongly associated with the development of HBV-related HCC. However, there are no Thai data on genotypic distribution and allele frequencies of rs17401966. Thai HBV patients seropositive for HBsAg (n=398) were therefore divided into two groups: a case group (chronic HBV with HCC; n=202) and a control group (HBV carriers without HCC; n=196). rs17401966 was amplified by polymerase chain reaction (PCR) and analyzed by direct nucleotide sequencing. The genotypic distribution of rs174019660 for homozygous major genotype (AA), heterozygous minor genotype (AG) and homozygous minor genotype (GG) in the case group was 49.5% (n=100), 40.1% (n=81) and 10.4% (n=21), respectively, and in controls was 49.5% (n=97), 42.3% (n=83) and 8.2% (n=16). Binary logistic regression showed that rs17401966 was not statistically associated with the risk of HCC development in Thai chronic HBV patients (p-value=0.998, OR=1.00 and 95% CI=0.68-1.48). In conclusion, the KIF1B gene SNP (rs174019660) investigated in this study showed no significant association with HBV-related HCC in Thai patients infected with HBV, indicating that there must be other mechanisms or pathways involved in the development of HCC.

Genetic alterations in hepatocellular carcinoma: An update

“…Therefore, it is important to evaluate the role of KIF1B rs17401966 in the genetic susceptibility to HCC and gene-environment interactions. Interestingly, three studies found that KIF1B rs17401966 was not associated with the development of HBV-related HCC in Thai, Japanese, and Saudi Arabian patients[85-87], and two other studies identified that KIF1B rs17401966 exerted protective effects against the susceptibility to HBV-related HCC in Chinese patients[88,89]. These inconsistencies might partly be because different ethnicities or study populations have distinct genetic architectures.…”

Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases

“…Genomic DNA was extracted from 100 µl peripheral blood mononuclear cells (PBMCs) using phenolchloroform-isoamyl alcohol isolation method as described previously (Sopipong et al, 2013). The quality of DNA was measured using spectrophotometer (NanoDrop 2000c, Thermo Scientific).…”

Host genetic variants influencing the clinical course of Hepatitis B virus infection

“…This might be explained by differences in the genetic diversity among Japanese, Korean, and Chinese populations or by multiple causative factors of hepatocarcinogenesis such as age, gender, environmental toxins, alcohol intake, HBV viral load, genotype, and distinct mutations. Other groups have also showed no association between the KIF1B variants and HBV‐related HCC in replication studies in Saudi Arabian and Thai ethnicities [Al‐Qahtani et al, ; Sopipong et al, ]. On the other hand, the KIF1B variants were not associated with susceptibility to chronic HBV infection in Chinese population, implying distinct genetic susceptibility factors might contribute to the progression from HBV infection to HCC [Zhong et al, ].…”