rs2070744 — NOS3 T-786C promoter

NOS3 T-786C Promoter - Controlling Enzyme Production

While rs1799983 affects the structure of the eNOS enzyme, the T-786C ¹¹ The -786 means 786 base pairs upstream of the gene's start; T-to-C is the nucleotide change promoter variant (rs2070744) controls how much enzyme is produced in the first place. This variant sits in the promoter region of the NOS3 gene, which is the DNA sequence that regulates gene transcription.

The Mechanism

The C allele at position -786 reduces NOS3 gene transcription by altering transcription factor binding. ²² Transcription factors are proteins that bind to specific DNA sequences to turn genes on or off A protein called replication protein A1 (RPA1) binds to the C allele more strongly, acting as a transcriptional repressor. The result is less eNOS mRNA, less protein, and ultimately less nitric oxide production capacity in your blood vessel walls. Studies have shown that the CC genotype reduces promoter activity by 30-40% compared to TT.

Compounding Effects

This promoter variant is particularly significant when combined with the Glu298Asp structural variant (rs1799983). Having both means you produce less enzyme (due to the promoter variant) AND the enzyme you do produce is less stable (due to the structural variant). ³³ This is analogous to a factory that both makes fewer units and has a higher defect rate on the ones it does make This compound effect can meaningfully reduce your nitric oxide availability.

Evidence and Clinical Relevance

Nakayama et al.⁴⁴ Nakayama et al.
Nakayama M et al. T-786C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation, 1999 found that the mutant allele was the most predictive independent risk factor for coronary spasm in a study of 174 patients and 161 controls. The CC genotype is associated with increased risk of coronary artery spasm, hypertension, and endothelial dysfunction in multiple populations.

Supporting Nitric Oxide Production

The strategies for supporting NO production are the same regardless of which NOS3 variant you carry: regular aerobic exercise (the most potent natural eNOS stimulator), dietary nitrates from vegetables (beets, spinach, arugula), adequate antioxidant intake to prevent eNOS uncoupling, and avoiding smoking, which directly damages endothelial function.