rs12252756 (NPS/FOXI2): Vascular Aging Variant

Key takeaways

• This variant near the NPS and FOXI2 genes was flagged as a suggestive signal for vascular aging in a Korean genome-wide association study.
• The association was measured using reactive hyperemia index (RHI), a non-invasive test of how well small blood vessels dilate.
• The study identified 64 genetic variants across 60 genes at the suggestive significance threshold, and this variant was among them.
• Evidence comes from a single cohort of 97 Korean adults and should be regarded as preliminary.
• No independent replication of this specific association has been reported in the available evidence.

What the research says A genome-wide association study (GWAS) of 97 Korean adults from the Namgaram project identified 64 genetic variants at suggestive significance (P < 5 x 10-5) for reactive hyperemia index (RHI), a non-invasive measure of vascular endothelial function (the capacity of blood vessel inner linings to dilate and regulate blood flow). rs12252756, near the NPS and FOXI2 genes, was among those 64 suggestive variants, which spanned 60 genes implicated in pathways including angiogenesis (new blood vessel formation), inflammatory response in blood vessels, and cardiovascular disease. The study also reported that putative protective alleles identified through the GWAS were significantly enriched in an independent population with decelerated vascular aging, and that putative causal genes showed differential mRNA expression in aging human primary endothelial cells.

Reported associations

• Vascular endothelial function (reactive hyperemia index): This variant was one of 64 hits reaching suggestive genome-wide significance (P < 5 x 10-5) for RHI in a Korean cohort of 97 adults; individual effect-size statistics for this specific variant were not reported separately in the source.

Evidence quality The evidence comes from a single GWAS published in Frontiers in Cardiovascular Medicine (2023), conducted in 97 Korean adults from the Namgaram project. The significance threshold used (P < 5 x 10-5) is a suggestive level, less stringent than the conventional genome-wide threshold of P < 5 x 10-8; three of the 60 candidate genes from the study did reach the stricter cutoff, but whether NPS or FOXI2 were among them cannot be confirmed from the available text. With only 97 participants, the study has limited statistical power, a higher risk of false-positive findings, and results that may not generalize beyond Korean ancestries. While putative protective alleles from this analysis were validated in an independent population with slower vascular aging, independent replication of this specific variant has not been documented. This evidence is preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.