HSPA8 Single-Nucleotide Polymorphism Is Associated with Serum HSC70 Concentration and Carotid Artery Atherosclerosis in Nonalcoholic Fatty Liver Disease

Genes (Basel). 2022 Jul 16;13(7):1265. doi: 10.3390/genes13071265.

Abstract

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima-media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

Keywords: cardiovascular disease; carotid artery ultrasound; liver biopsy; precision medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis* / genetics
  • Carotid Arteries
  • Carotid Artery Diseases* / genetics
  • Carotid Intima-Media Thickness
  • HSC70 Heat-Shock Proteins
  • Humans
  • Male
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Polymorphism, Single Nucleotide

Substances

  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human

Grants and funding

This work was supported by JSPS Grant-in-Aid for Young Scientists number 18K15754 and internal budget of Saga University Hospital for advanced medical technology.