rs1169310 (HNF1A): C-Reactive Protein Variant
Key takeaways
- Variants in HNF1A, a liver transcription factor, have been independently linked to blood CRP levels (an inflammation marker) in two separate cohort studies
- The alternate allele at rs1169310 reduces C12orf43 expression across eight tissues, including heart, arteries, and skeletal muscle
- GTEx data from up to 953 donors show these expression effects reach p values as low as 6.8 x 10^-17, indicating a statistically strong signal
- Effect sizes at this locus may differ across ancestries, and research in diverse populations is key to understanding the full genetic picture
- The biological function of C12orf43 is not described in the current evidence base for this variant
Key takeaways
- rs1169310 is located near two genes: C12orf43 (chromosome 12 open reading frame 43) and HNF1A (hepatocyte nuclear factor-1 alpha, a protein that controls gene activity in the liver)
- Variants in HNF1A have been independently linked to plasma C-reactive protein (CRP) levels, a blood marker of inflammation, in two separate cohort studies
- The alternate allele at this position is associated with reduced C12orf43 expression across at least eight tissue types, including heart, arteries, and skeletal muscle
- Effect sizes at this locus may differ across ancestries, and research in diverse populations is key to understanding the full genetic picture
- The biological function of C12orf43 is not described in the current evidence base for this variant
What the research says Polymorphisms in HNF1A, specifically within a 5 kilobase (kb) region of its first intron (a non-coding segment embedded in the gene), were independently associated with plasma CRP concentration in two cohorts: the Pharmacogenomics and Risk of Cardiovascular Disease (PARC) study and the Cardiovascular Health Study (CHS). The Population Architecture using Genomics and Epidemiology (PAGE) study, which enrolled 49,839 non-European participants across Hispanic/Latino, African American, Asian, Native Hawaiian, and Native American groups, demonstrated that effect-size heterogeneity across ancestries is common at known GWAS (genome-wide association study) loci, and that diverse-population analyses uncover signals missed by European-ancestry-only research. GTEx v11 data from up to 953 donors identify rs1169310 as a cis-eQTL (a variant that influences the expression level of a nearby gene) for C12orf43, with the alternate allele reducing expression in eight tissues at p values between 6.0 x 10^-12 and 6.8 x 10^-17 GTEx Portal.
Reported associations
- C-reactive protein (CRP) levels: Polymorphisms in HNF1A intron 1 are associated with plasma CRP, with independent replication across the PARC and CHS cohorts
- C12orf43 gene expression: The alternate allele reduces expression across eight tissue types, with the strongest signal in tibial artery (p = 6.8 x 10^-17, n up to 953 donors) GTEx Portal
Evidence quality The HNF1A-CRP association is supported by independent replication in two distinct cohorts (PARC and CHS), increasing confidence beyond a single study. However, the available report describes "several SNPs within a 5 kb region of HNF1A intron 1" without providing specific effect sizes, p-values, or sample sizes for rs1169310 individually, making this a regional rather than confirmed single-variant finding. The PAGE study (n = 49,839) highlights that genetic effect sizes at known GWAS loci can differ across ancestries and that non-European populations remain underrepresented in genomic research, which is relevant for interpreting any result derived from non-diverse cohorts. The GTEx eQTL data are statistically robust (p values up to 6.8 x 10^-17 across up to 953 donors) and consistent in direction across all eight tissues, but an eQTL result establishes a link to gene expression levels rather than to any health outcome.
Tissue-specific expression effects
- C12orf43: The alternate allele is linked to reduced expression across eight tissues: heart atrial appendage (p = 8.7 x 10^-13), tibial artery (p = 6.8 x 10^-17), subcutaneous adipose (p = 1.6 x 10^-11), aorta (p = 1.1 x 10^-10), esophagus muscularis (p = 1.3 x 10^-10), tibial nerve (p = 3.8 x 10^-11), cultured fibroblasts (p = 3.4 x 10^-11), and skeletal muscle (p = 6.0 x 10^-12); all effects are in the direction of reduced expression GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does HNF1A do?
HNF1A (hepatocyte nuclear factor-1 alpha) is a transcription factor, meaning it is a protein that controls the activity of other genes. It is most active in the liver. Common variants in this gene have been associated with plasma C-reactive protein levels, a standard blood marker of inflammation.
What is C-reactive protein (CRP) and why does it matter genetically?
C-reactive protein is produced by the liver and circulates in the blood as a general indicator of inflammation. Genetic variants near HNF1A have been associated with baseline CRP levels, suggesting these variants influence how the liver regulates this inflammatory protein.
What is C12orf43?
C12orf43 (chromosome 12 open reading frame 43) is a gene located near HNF1A on chromosome 12. GTEx data show that the alternate allele at rs1169310 reduces C12orf43 expression across eight tissues, but the specific biological function of C12orf43 is not described in the studies available for this variant.
Does rs1169310 affect heart or cardiovascular health?
The studies provided do not directly link rs1169310 to heart disease outcomes. However, this variant is associated with CRP (an inflammation marker frequently measured in cardiovascular research) and shows reduced C12orf43 expression in heart atrial appendage tissue and arteries in GTEx data. No causal link to cardiac outcomes is established by the current evidence.
Does this variant work the same way across different ancestries?
Research in diverse populations shows that genetic effect sizes and allele frequencies commonly differ across ancestries. The PAGE study, which enrolled nearly 50,000 non-European participants, found that associations discovered in European populations do not always generalize directly, and that diverse-cohort analyses are essential for accurate genetic effect estimation.