Complement component 3 haplotypes influence serum complement activity and milk production traits in Chinese Holstein cattle

PLoS One. 2022 Jun 30;17(6):e0268959. doi: 10.1371/journal.pone.0268959. eCollection 2022.

Abstract

Complement component 3 (C3) is the key molecule of the three pathways of complement activation (alternative, classical, and lectin pathways), which are involved in phagocytosis, inflammation, and immunoregulation processes to destroy infectious microorganisms. In this study, three novel single-nucleotide polymorphisms (SNPs) (g.-1293C>G located in the 5'-flanking region, g.56T>C in exon I, and g.7017C>T in exon XII) of the C3 gene were detected using created restriction site polymerase chain reaction, restriction fragment length polymorphism, and DNA sequencing in 952 cattle from three Chinese breeds. The genotypes and haplotypes were analyzed to investigate the polymorphisms and their possible implications, with particular investigative focus on their associations with serum C3 level, complement hemolytic activity (CH50 and ACH50), and milk production traits. The g.56T>C SNP in exon I affected the serum ACH50 (P<0.01) and the milk somatic cell score (SCS) (P<0.05), and the g.7017C>T SNP in exon XII significantly affected the serum ACH50 values (P<0.01). Moreover, statistical analyses revealed that individuals with genotypic combination CCC/GCC showed significantly lower SCS and the lowest C3 concentration in serum compared with cows with CCC/GTT (P = 0.0007) and CTT/CTT (P = 0.0021); the individuals with CCC/CCT had significantly higher ACH50 values than those with CCC/CTC (P = 0.0008) and CTC/GTC (P = 0.001); cows with CCT/CTT had higher values of CH50 and 305-day milk yield (P>0.05). The C3 expression levels were significantly increased in lung and mammary tissues (P<0.05), while significantly decreased in heart, spleen, liver, and kidney tissues in mastitis cows compared with those in healthy animals (P<0.01), respectively. Bacterial counts of serum antibacterial activities were also completed to verify the effect of SNPs on resistance to mastitis pathogens. Genetically resistant cows (CCC/GCC) had serum with noticeably higher antibacterial activity against S. aureus and E. coli in vitro than the genetically susceptible CCC/GTT cows (P<0.05). Results from this study imply that the C3 gene plays a role in resistance to bacterial infection and that it can be used as a molecular marker for complement activity and traits related to milk production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Cattle
  • China
  • Complement C3 / genetics
  • Complement C3 / metabolism
  • Escherichia coli
  • Female
  • Genotype
  • Haplotypes
  • Lactation / physiology
  • Mastitis* / metabolism
  • Milk* / metabolism
  • Polymorphism, Single Nucleotide
  • Staphylococcus aureus

Substances

  • Anti-Bacterial Agents
  • Complement C3

Grants and funding

This research was funded by the National Natural Science Foundation of China (grant no. 31671287), Taishan Leading Industry Talents – Agricultural Science of Shandong Province (grant no. LJNY201713), Shandong Province Modern Agricultural Technology System Donkey Industrial Innovation Team (grant no. SDAIT-27), and the Open Project of Shandong Collaborative Innovation Center for Donkey Industry Technology (grant no.3193308). Changfa Wang is a funder of all funds and the corresponding author of this paper. He played an important role in study design, analysis, decision to publish, or preparation of the manuscript.