High frequency of the PNPLA3 rs738409 [G] single‐nucleotide polymorphism in Hmong individuals as a potential basis for a predisposition to chronic liver disease

• Published in: Cancer 2018-04, Vol.124 (S7), p.1583-1589
• Main Authors: Tepper, Clifford G., Dang, Julie H. T., Stewart, Susan L., Fang, Dao M., Wong, Kimberly A., Liu, Stephenie Y., Davis, Ryan R., Dao, Doan Y., Gregg, Jeffrey P., Török, Natalie J., Chen, Moon S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Asian Americans - genetics; California - epidemiology; Cancer; carrier rate; Chronic Disease; Cirrhosis; Confidence intervals; Deoxyribonucleic acid; DNA; Etiology; Fatty liver; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genomes; Genotype; Genotyping; Health risks; Hepatitis; Hepatocellular carcinoma; High frequencies; Hmong; Hmong people; Humans; Incidence; Lipase - genetics; Liver; Liver cancer; Liver cirrhosis; Liver Cirrhosis - epidemiology; Liver Cirrhosis - genetics; Liver diseases; Male; Membrane Proteins - genetics; Metabolic syndrome; Middle Aged; nonalcoholic steatohepatitis (NASH); Oncology; patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) rs738409; Phospholipase; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Risk analysis; Risk factors; Single-nucleotide polymorphism; Young Adult
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31122

BACKGROUND An exploratory study was performed to determine the prevalence of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) rs78409 [G] allele among the Hmong as a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic liver disease and is expected to replace viral hepatitis as the leading cause of cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all populations in California, the Hmong experience the highest risk of death from HCC and the highest prevalence of metabolic syndrome risk factors among Asians that predispose them to NAFLD. Here a genetic explanation was sought for the high rates of chronic liver disease among the Hmong. The literature pointed to the PNPLA3 rs738409 [G] allele as a potential genetic culprit. METHODS Cell‐free DNA was isolated from 26 serum samples previously collected in community settings. Quantitative polymerase chain reaction–based single‐nucleotide polymorphism (SNP) genotyping was performed with a validated TaqMan SNP genotyping assay, and results were analyzed with TaqMan Genotyper software. RESULTS The PNPLA3 rs738409 [C>G] variant occurred at a frequency of 0.46 (12 of 26; 95% confidence interval, 0.27‐0.67). This carrier rate would rank the Hmong as the third highest population in the 1000 Genomes Project. CONCLUSIONS Although this small sample size limits the generalizability, the high frequency rates of this allele along with the presence of metabolic syndrome risk factors warrant further studies into the etiology of NAFLD among the Hmong. Cancer 2018;124:1583‐9. © 2018 American Cancer Society. The patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) rs738409 [G] allele has been cited as a potential genetic explanation for nonalcoholic steatohepatitis, a potential risk factor for hepatocellular carcinoma. The prevalence of this allele is 0.46 (95% confidence interval, 0.27‐0.67) in an exploratory study of 26 Hmong samples; therefore, further study is warranted for ascertaining the role of this variant in the etiology of nonalcoholic steatohepatitis in this population.