SNP associations in the L-citrulline metabolic pathway and vascular aging in the Japanese population

Figures

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  Fig 1. Comparison of questionnaire scores among genotypes for the significant associations. To facilitate an intuitive understanding of the effect of SNPs in the candidate gene analysis, the means for each genotype were visualized as a bar graph. The mean questionnaire scores were compared across the SNP genotypes for those with significant associations with the corresponding traits. For both traits, the population with homozygous minor allele was the most symptomatic, followed by the heterozygous (major and minor alleles) population. The x-axis represents the genotypes for each SNP, arranged from left to right as follows: homozygous major allele, heterozygous, and homozygous minor allele. The y-axis shows either the mean of SF-36 scores or VAS scores used for defining each trait. For body pain, SF-36 scores are shown, where lower scores indicate more severe pain. For all other traits, VAS scores are displayed. Error bars indicate standard error of mean.

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  Fig 2. Summary of sites of activity of genes encoded by SNPs observed to be associated in our study in the NO signaling pathway downstream of Cit. The sites of activity of genes containing SNPs observed to be associated in our study in the pathway where Cit contributes to vascular flexibility and expandability (NO signaling pathway) are indicated. Genes with observed associations (SNPs that were associated in parentheses) are indicated in green letters, and symptoms of vascular aging that were observed to be associated with that gene (SNP) are indicated near the gene name in red letters. Arg conversion to NO is the first step in the NO signaling pathway, and it is critical to increase the activity of NOS and inhibit the activity of protein Arg methyltransferase inhibitor (PRMT) in increasing NO production. In addition, downstream NO signaling must lead to sGC-cGMP-mediated regulation of intracellular Ca2 + concentrations via PKG or protein kinase A (PKA) to correctly contribute to vascular flexibility and expandability. PDE, ADCY, and KCNMB play an important role in these pathways. NOS: NO synthase, sGC-cGMP: soluble guanylate cyclase –cyclic guanosine monophosphate, PKG: cGMP-dependent…