rs111841972 (C9orf43): Blood Pressure and Gene Expression
Key takeaways
- rs111841972, near C9orf43 on chromosome 9, appears in blood pressure studies covering more than one million participants.
- This variant reduces expression of POLE3, a DNA replication gene, across six tissues including heart and artery.
- The same variant increases RGS3 activity in pancreas while reducing it in whole blood, showing tissue-specific effects.
- RGS3 regulates G protein signaling pathways linked to heart rate and blood vessel tone, making this a biologically plausible blood pressure candidate.
- No lifestyle-specific findings have been recorded for this variant.
Key takeaways
- rs111841972, near C9orf43 on chromosome 9, appears in blood pressure studies covering more than one million participants.
- This variant reduces expression of POLE3, a DNA replication gene, across six tissues including heart and artery.
- The same variant increases RGS3 activity in pancreas while reducing it in whole blood, showing tissue-specific effects.
- RGS3 regulates G protein signaling pathways linked to heart rate and blood vessel tone, making this a biologically plausible blood pressure candidate.
- No lifestyle-specific findings have been recorded for this variant.
What the research says Two of the largest blood pressure genome-wide association studies conducted to date, one in n=1,028,980 European-ancestry individuals and another in up to n=1,319,000 participants, mapped genetic influences on systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure across the genome, including the chromosome 9 region where rs111841972 is located. GTEx eQTL (expression quantitative trait locus, a variant that influences how much of a specific gene is produced in a given tissue) data from 953 donors shows that the alternate allele at this locus consistently reduces expression of POLE3 (DNA Polymerase Epsilon Subunit 3, a component of the DNA replication machinery) across six tissues, with particularly strong effects in thyroid and visceral adipose tissue, while simultaneously increasing RGS3 (Regulator of G protein Signaling 3) expression in pancreas and reducing it in whole blood. GTEx Portal
Reported associations
- Blood pressure traits: This variant resides on chromosome 9 in a region covered by large blood pressure genome-wide analyses; one study (n=1,028,980) identified 2,103 independent genetic signals for SBP, DBP, and pulse pressure including 113 novel loci, while a second study (up to n=1,319,000) identified 106 new BP-associated regions and 87 rare variant associations. The available study text does not name this specific variant as a confirmed significant signal.
- POLE3 expression (multi-tissue): The alternate allele at this locus is associated with reduced POLE3 expression across thyroid, visceral adipose, tibial nerve, heart atrial appendage, aorta, and subcutaneous adipose tissue. GTEx Portal
- RGS3 expression (tissue-specific): The alternate allele at this locus is associated with increased RGS3 expression in pancreas and reduced RGS3 expression in whole blood. GTEx Portal
Evidence quality The GTEx eQTL associations are well-powered, based on 953 donors with all associations passing a false discovery rate threshold (FDR < 0.05), and show directionally consistent effects on POLE3 across all six tissues tested. The blood pressure context derives from two of the largest BP genome-wide association studies published, but the provided study text does not explicitly name rs111841972 as a significant variant, so the strength of a direct BP association for this locus alone cannot be confirmed from the available sources. There are no conflicting findings within the provided data. The opposing RGS3 effects across tissues (increased in pancreas, decreased in whole blood) are an observation from eQTL data without further mechanistic explanation in the available sources; eQTL effects indicate a potential mechanism and do not on their own establish a causal role in blood pressure regulation.
Tissue-specific expression effects
- POLE3: The alternate allele at this locus is linked to reduced POLE3 expression across six tissues, with the most pronounced effects in thyroid and visceral adipose tissue, and additional effects in tibial nerve, heart atrial appendage, aorta, and subcutaneous adipose; all associations pass FDR-based statistical thresholds. GTEx Portal
- RGS3: The alternate allele is linked to increased RGS3 expression in pancreas and reduced RGS3 expression in whole blood, indicating tissue-dependent regulation of this G protein signaling gene. GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs111841972 and what gene is it near?
rs111841972 is a genetic variant located near the C9orf43 gene on chromosome 9. It has been included in large-scale genome-wide analyses of blood pressure traits.
Is rs111841972 linked to blood pressure?
This variant lies in a chromosomal region covered by large blood pressure genome-wide association studies with over one million participants. Its effects on RGS3, a gene involved in cardiovascular signaling, provide a biological rationale, though the available study reports do not confirm this specific variant as a named blood pressure locus.
What does this variant do to POLE3 gene expression?
GTEx data from 953 donors shows this variant is associated with reduced POLE3 expression across six tissues: thyroid, visceral adipose, tibial nerve, heart atrial appendage, aorta, and subcutaneous adipose. POLE3 is a component of the DNA replication machinery.
What is RGS3 and why might it be relevant to blood pressure?
RGS3 stands for Regulator of G protein Signaling 3. It helps control how cells respond to G protein-coupled receptor signals, including pathways that regulate heart rate and blood vessel tone. This variant increases RGS3 expression in the pancreas while reducing it in whole blood.
What does C9orf43 do?
C9orf43, or Chromosome 9 Open Reading Frame 43, is a gene on chromosome 9 whose function is not fully characterized in the available sources. Nearby genes POLE3 and RGS3, whose expression is influenced by this variant, have more defined roles in DNA replication and G protein signaling respectively.