DPEP1
This gene codes for a kidney enzyme involved in amino acid metabolism 1. Interestingly, this protein has a newly identified separate function to recruit innate immune cells (neutrophils) to inflamed lung and liver 2. Different SNPs linked with this gene have been associated with levels of various metabolites, importantly, including homocysteine, as well as a number of other conditions.
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) |
|---|---|---|---|
| rs154657 | g | a | 40 |
Risk Description
This common non-coding variant has been associated with homocysteine levels in the blood 3. rs154657 maps to a gene-rich locus and has been associated with the expression levels and splicing of multiple genes. The DPAP1 gene coding for Dipeptidase 1 is a potentially causal candidate 4, since DPAP1 deficiency results in increased urinary excretion of homocysteine’s precursor, cysteine 5 6.
However, the exact mechanisms of this effect are not yet known, and it is possible that other genes mediate the association of rs154657 with homocysteine levels.
Nutritional Contraindications:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| SAM-e Supplements | S-adenyosylmethionine |
The risk allele ‘A’ of G89641688A may lead to a build up of S-adenosylhomocysteine inhibiting the production of SAM-e. Therefore SAM-e supplementation could be beneficial, although care should be taken to not oversaturate an already overloaded pathway as this may lead to further complications. |
Discuss this information with your doctor before taking any course of action.
Citations:
- Allison SJ. DPEP1 and CHMP1A in kidney ferroptosis. Nat Rev Nephrol. 2021 Nov;17(11):707. doi: 10.1038/s41581-021-00496-2. PMID: 34561671.
- Choudhury SR, Babes L, Rahn JJ, Ahn BY, Goring KR, King JC, Lau A, Petri B, Hao X, Chojnacki AK, Thanabalasuriar A, McAvoy EF, Tabariès S, Schraeder C, Patel KD, Siegel PM, Kopciuk KA, Schriemer DC, Muruve DA, Kelly MM, Yipp BG, Kubes P, Robbins SM, Senger DL. Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver. Cell. 2019 Aug 22;178(5):1205-1221.e17. doi: 10.1016/j.cell.2019.07.017. PMID: 31442408.
- van Meurs JB, Pare G, Schwartz SM, et al. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. The American Journal of Clinical Nutrition. 2013 Sep;98(3):668-676. DOI: 10.3945/ajcn.112.044545. PMID: 23824729; PMCID: PMC4321227.
- Paré G, Chasman DI, Parker AN, Zee RR, Mälarstig A, Seedorf U, Collins R, Watkins H, Hamsten A, Miletich JP, Ridker PM. Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women’s Genome Health Study. Circ Cardiovasc Genet. 2009 Apr;2(2):142-50. doi: 10.1161/CIRCGENETICS.108.829804. PMID: 20031578; PMCID: PMC2745176.
- Mayatepek E, Badiou S, Bellet H, Lehmann WD. A patient with neurological symptoms and abnormal leukotriene metabolism: a new defect in leukotriene biosynthesis. Ann Neurol. 2005 Dec;58(6):968-70. doi: 10.1002/ana.20687. PMID: 16315285.
- Finkelstein JD. Inborn errors of sulfur-containing amino acid metabolism. J Nutr. 2006 Jun;136(6 Suppl):1750S-1754S. doi: 10.1093/jn/136.6.1750S. PMID: 16702350.