Chronic low-grade inflammation is the common biological thread linking cardiovascular disease, neurodegeneration, metabolic syndrome, and accelerated aging.
The genetic architecture of your inflammatory set-point. Six cytokine regulators and the primary mitochondrial antioxidant enzyme.
The Biology
Acute inflammation is protective and essential. Chronic systemic inflammation. Maintained at a low but persistent level by genetic variants that keep cytokine production elevated. Is associated with virtually every major age-related disease. The interplay between pro-inflammatory cytokines (IL-6, IL-1α, IL-1β, TNF-α) and anti-inflammatory regulators (IL-10) determines your baseline inflammatory tone. Separately, your mitochondria continuously produce reactive oxygen species as a byproduct of energy production; superoxide dismutase 2 is the primary mitochondrial antioxidant enzyme that neutralizes them.
What Varia Analyzes
Seven variants covering both sides of the inflammatory balance. IL-6 promoter (rs1800795), which governs baseline IL-6 transcription; IL-1α (rs1800587) and IL-1β (rs1143634, rs16944), which regulate two primary pro-inflammatory cytokines; IL-10 promoter (rs1800896), the key anti-inflammatory counterregulator; TNF-α promoter (rs1800629), a master regulator of systemic inflammatory response; and SOD2 Val16Ala (rs4880), which determines the mitochondrial import efficiency of the primary mitochondrial antioxidant enzyme, manganese superoxide dismutase.
Why It Matters
The IL-6 finding has specific longevity implications. Chronically elevated IL-6 is associated with reduced lifespan in population studies. The SOD2 Ala/Ala genotype reduces mitochondrial MnSOD import efficiency and is associated with elevated mitochondrial oxidative stress. Relevant to anyone pursuing mitochondrial health optimization. Reading pro-inflammatory and anti-inflammatory variants together gives a more complete picture: someone who is an IL-6 high-producer and IL-10 low-producer faces a compounding inflammatory burden not visible from either finding alone.
Key sources
- Fishman D, et al. The effect of novel polymorphisms in the interleukin-6 gene on IL-6 transcription and plasma IL-6 levels. J Clin Invest. 1998.
- Bonafè M, et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol. 2001.
- Wilson AG, et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. PNAS. 1997.
- Sutton A, et al. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics. 2003.