How are "Serum Branched-chain Amino Acid Levels" encoded by the genome?
Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential acids for your body, but unlike other properties in the body, they cannot be produced and come from what we eat. BCAA supports muscle functions and muscle growth and has been studied in a number of muscle wasting disorders for more than 50 years. Elevated serum levels of BCAAs are associated with metabolic dysfunction.
Branched-chain a-ketoacid dehydrogenase complex (BCKDC) is the key enzyme that catalyzes the first irreversible step in the BCAA metabolism, and the phosphorylation of branched-chain a-ketoacid dehydrogenase kinase (BCKDK) can inhibit the activity of BCKDC. Conversely, BCKDC is activated by the mitochondrial isoform of PP2C domain-containing protein phosphatase 1K (PPM1K). A randomization analysis of 16,596 Caucasians showed that the PPM1K rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) were associated with serum leucine and valine levels, and rs7678928 SNP was associated with serum isoleucine level.
However, because of the focus on one ethnicity, researchers began to study the effects on the chinese population as well. Researchers investigated the effects of rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) in the PPM1K gene on the serum branched-chain amino acids levels in 234 Chinese individuals who were randomly recruited from the Diabetes Prevention Programme. Results showed that the serum valine and total BCAA levels in subjects with CC genotype in rs1440581 were higher than in those with TT genotype, which was consistent with findings from the study in Caucasians. This indicates that the C-allele of rs1440581 may be responsible for increasing circulating BCAA levels in the Chinese population. The rs1440581 polymorphism seems to affect PPM1K expression in Chinese, lowering PPM1K activity in C allele carriers. Therefore serum BCAAs accumulate by affecting the branched-chain a-ketoacid dehydrogenase complex (BCKDC) activity.
An increased serum level is important because previous research has linked it to diseases like heart disease. Further investigation is needed to determine if the rs1440581 and rs7678928 polymorphisms have a causal relationship with the risk of heart disease. If you would like to know more about this research, you can read the study here:
https://pubmed.ncbi.nlm.nih.gov/34382495/
Are you interested in learning more about your genetic tendency for serum branched-chain amino acid levels? You can log in to your Genomelink TRAITS to see this new genetic trait.
