Expressive

rs12228810 (AACS): Resistant Hypertension Variant

Key takeaways

  • rs12228810 in the BRI3BP-AACS region was examined in a genome-wide study of resistant hypertension, a condition requiring four or more medications to control blood pressure.
  • The ALT allele at this variant is consistently linked to reduced AACS gene expression in five tissues: brain cerebellum, cerebellar hemisphere, skeletal muscle, sigmoid colon, and heart left ventricle.
  • The same ALT allele also reduces expression of neighboring gene ENSG00000279233 in prostate, skeletal muscle, and tibial nerve.
  • The resistant hypertension GWAS was limited to White and Hispanic participants (n=1,779 total), so findings may not apply broadly.
  • No lifestyle or dietary factors specific to this variant have been reported in available studies.

Key takeaways

  • rs12228810 in the BRI3BP-AACS region was examined in a genome-wide study of resistant hypertension, a condition requiring four or more medications to control blood pressure.
  • The ALT allele at this variant is consistently linked to reduced AACS gene expression in five tissues: brain cerebellum, cerebellar hemisphere, skeletal muscle, sigmoid colon, and heart left ventricle.
  • The same ALT allele also reduces expression of neighboring gene ENSG00000279233 in prostate, skeletal muscle, and tibial nerve.
  • The resistant hypertension GWAS was limited to White and Hispanic participants (n=1,779 total), so findings may not apply broadly.
  • No lifestyle or dietary factors specific to this variant have been reported in available studies.

What the research says A genome-wide association study (GWAS) of resistant hypertension (RHTN) - defined as blood pressure uncontrolled on three or more antihypertensive drugs, or controlled only with four or more - enrolled 1,194 White and Hispanic participants with hypertension and coronary artery disease (INVEST-GENES cohort), with replication in 585 comparable participants (SPS3-GENES cohort), and examined variants across the genome including the BRI3BP-AACS locus (El Rouby et al., The pharmacogenomics journal, 2020). GTEx v11 expression data from 953 donors shows the ALT allele at rs12228810 is associated with reduced AACS expression in five tissues and reduced expression of ENSG00000279233 in three additional tissues GTEx Portal.

Reported associations

  • Resistant hypertension: Examined in a GWAS of RHTN (El Rouby et al., The pharmacogenomics journal, 2020; discovery n=1,194, replication n=585, White and Hispanic participants); the study's top replicated genome-wide significant signals were in MSX2 (OR=1.60, p=3.8 x 10^-8), IFLTD1 (OR=1.90), and PTPRD (OR=1.60); a specific effect size for rs12228810 is not reported in the available published text.
  • AACS gene expression - brain: The ALT allele is associated with reduced AACS expression in brain cerebellum and cerebellar hemisphere GTEx Portal.
  • AACS gene expression - skeletal muscle, colon, and heart: The ALT allele is associated with reduced AACS expression in skeletal muscle, sigmoid colon, and heart left ventricle GTEx Portal.
  • ENSG00000279233 gene expression: The ALT allele is associated with reduced expression of ENSG00000279233 in prostate, skeletal muscle, and tibial nerve GTEx Portal.

Evidence quality The GTEx eQTL evidence is based on 953 donors with FDR < 0.05 across five tissues for AACS and three tissues for ENSG00000279233, representing a consistent multi-tissue expression signal GTEx Portal. The RHTN GWAS (El Rouby et al., The pharmacogenomics journal, 2020) used a discovery cohort of 1,194 and a replication cohort of 585 participants, which is modest by current GWAS standards; enrollment was restricted to White and Hispanic participants, limiting ancestry generalizability. The study's top genome-wide significant hits were in MSX2, IFLTD1, and PTPRD; rs12228810 is not listed among the primary replicated results in the available published text, making any direct link to the RHTN phenotype for this locus preliminary and unconfirmed.

Tissue-specific expression effects

  • AACS: Reduced expression in brain cerebellum, cerebellar hemisphere, skeletal muscle, sigmoid colon, and heart left ventricle for carriers of the ALT allele GTEx Portal.
  • ENSG00000279233: Reduced expression in prostate, skeletal muscle, and tibial nerve for carriers of the ALT allele GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • Hypertension risk management strategies Moderate

    Genetic variant increases resistant hypertension risk; early intervention may prevent disease progression

Lifestyle

  • Cardiovascular risk reduction activities Moderate

    Low sodium intake and regular exercise are standard hypertension prevention; genetic risk makes adherence more important

    150 min moderate cardio weekly, limit sodium to <2300mg daily

Screening

  • Blood pressure screening Moderate

    rs12228810 C allele increases resistant hypertension risk (OR=1.087)

    Check blood pressure at least annually, starting by age 30

Frequently asked questions

What is the BRI3BP-AACS gene region?

BRI3BP and AACS are neighboring genes on the same chromosomal region. GTEx expression data shows that the rs12228810 variant in this region is associated with changes in how much AACS and a neighboring gene are expressed across brain, heart, muscle, and other tissues.

Is rs12228810 linked to resistant hypertension?

This variant was included in a genome-wide association study of resistant hypertension, a form of high blood pressure that requires four or more medications to control. However, rs12228810 is not listed among the top genome-wide significant hits in that study, so any link to resistant hypertension for this specific variant is preliminary and unconfirmed.

What does it mean that this variant reduces AACS gene expression?

GTEx data shows the ALT allele at rs12228810 is associated with lower AACS gene activity in brain, heart, muscle, and colon. This is a molecular observation about gene regulation in those tissues; whether it influences health outcomes requires further study.

Which tissues are affected by rs12228810?

GTEx data links the ALT allele to reduced AACS expression in brain cerebellum, cerebellar hemisphere, skeletal muscle, sigmoid colon, and heart left ventricle. The same allele also reduces expression of ENSG00000279233 in prostate, skeletal muscle, and tibial nerve.

How reliable is the evidence for rs12228810?

The cross-tissue eQTL evidence from GTEx is based on 953 donors with strict statistical thresholds and is considered robust for tissue expression patterns. The resistant hypertension GWAS had a relatively small sample (n=1,779) and did not report rs12228810 among its primary genome-wide significant results.