Correlation study on chromogranin A genetic polymorphism and prognosis of critically ill patients

J Crit Care. 2017 Jun:39:137-142. doi: 10.1016/j.jcrc.2017.02.015. Epub 2017 Feb 13.

Abstract

Objective: The objective was to investigate the correlation between single nucleotide polymorphism (SNP) of chromogranin A (CHGA) and prognosis of critically ill patients.

Methods: We screened 357 critically ill patients consecutively admitted to our intensive care unit. The -89/-415/-462 SNP locus in the promoter region and the +9559/+9578/+9590/+9611 SNP locus in exon 7 coding of CHGA were genotyped by polymerase chain reaction and DNA sequencing technology. Subsequently, the correlation between genotype and prognosis of patients was analyzed.

Results: (1) Three hundred critically ill Chinese Han patients were enrolled in the study. CHGA-415/-462/+9559/+9611 SNPs were polymorphically distributed. Phenotypes of the 4 SNPs were shown not to be in linkage disequilibrium, and there were no significant differences in the minor allele frequencies (MAFs) of the 4 SNPs between participants of this study and healthy people in Asia. (2) The CHGA-415 T/C MAF of the nonsurvival group was significantly higher than that of the survival group (MAF 0.3813 and 0.2864, respectively; P=.026). Survival analysis showed that there were significant differences between the CHGA-415 T/C mutation group (including TC and CC genotypes) and the wild-type group (TT genotype) (log rank=8.887, P=.003). The mortality in the mutant group was significantly higher than that in the wild-type group (0.3333 and 0.1852, respectively; P=.004). (3) Binary logistic analysis showed that CHGA-415 T/C polymorphism was an independent risk factor for the mortality of critically ill patients (odds ratio, 2.286; 95% confidence interval, 1.165-4.484; P=.016).

Conclusions: Critically ill patients with CHGA-415 T/C mutant genotype display higher 30-day mortality than those with the wild-type group. CHGA-415 T/C polymorphism is an independent risk factor of poor prognosis in critically ill Chinese Han patients.

Keywords: Chromogranin A; Critically ill patients; Minor allele frequency; Prognosis; Single nucleotide polymorphism.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • China / ethnology
  • Chromogranin A / genetics*
  • Critical Illness*
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Factors

Substances

  • CHGA protein, human
  • Chromogranin A