The GUCY1A3 gene contains – like most genes – thousands of genetic variants (SNPs). However, the vast majority of these variants have no known functional impact on gene activity or on the resulting protein. Research therefore focuses on those variants that are biologically plausible (e.g. located in regulatory gene segments), that correlate significantly with a clinical trait in large population-based studies (e.g. GWAS), and that have been replicated – that is, confirmed again in independent studies.
The variant rs7692387 (G > A) meets precisely these criteria. It lies in the promoter region of the GUCY1A3 gene – the section that controls gene activity. Studies (Hall et al., European Heart Journal, 2019; Kessler et al., Cardiovascular Research, 2019) show that this variant can influence the expression of soluble guanylate cyclase and thereby modulate the response to acetylsalicylic acid (ASA).
To date, rs7692387 is the only variant whose association with the effect of ASA has been demonstrated in a scientifically reproducible way. The GUCY1A3 gene mutation, which can influence your response to acetylsalicylic acid (ASA) and your cardiovascular health, is therefore specifically analysed.
Other SNPs in the GUCY1A3 gene or in neighbouring genes (e.g. GUCY1B3) have also been described, but their influence on the effect of ASA has so far not been clearly demonstrated.
The GUCY1A3 gene encodes a subunit of soluble guanylate cyclase, an enzyme in the nitric oxide (NO) signalling pathway that is essentially involved in the regulation of vascular tone and platelet function – that is, precisely in the area where ASA acts.
Studies show that this variation can influence the individual response to acetylsalicylic acid (ASA):
Kathryn T. Hall et al. (2019). Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin. European Heart Journal, 40(41), 3385‑3392.
Thorsten Kessler et al. (2019). Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention. Cardiovascular Research, 115(10), 1512‑1518.