Expressive

rs11810574 (FMN2): HCTZ Metabolic Response

Key takeaways

  • rs11810574 is a variant near FMN2 whose ALT allele reduces FMN2 expression in cultured fibroblast cells.
  • This variant appears in a genome-wide study of metabolic side effects from hydrochlorothiazide (HCTZ), one of the most widely prescribed blood pressure medications.
  • The HCTZ GWAS found a genome-wide significant hit in the NELL1 gene for triglyceride changes in African American patients; specific results for rs11810574 are not reported in available study text.
  • The expression finding from GTEx v11 (953 donors, FDR<0.05) is the most thoroughly documented result currently available for this variant.

Key takeaways

  • rs11810574 is a variant near the FMN2 gene, identified in a genome-wide association study (GWAS) of adverse metabolic effects from the blood pressure medication hydrochlorothiazide (HCTZ).
  • The ALT allele at this position is linked to reduced FMN2 expression in cultured fibroblast cells, based on GTEx expression data from 953 donors.
  • The primary genome-wide significant finding from the associated GWAS pointed to the NELL1 gene for triglyceride changes in African Americans; specific results for rs11810574 are not reported in the available study text.
  • Overall evidence for this variant is preliminary and limited to a single GWAS context and one tissue type in expression data.

What the research says GTEx v11 eQTL analysis across 953 donors shows the ALT allele at rs11810574 is associated with reduced FMN2 expression in cultured fibroblasts (slope -0.33, p=7.5e-6, FDR<0.05) GTEx Portal. A GWAS examining changes in fasting plasma glucose and triglycerides following HCTZ treatment in African American patients with mild-to-moderate primary hypertension - drawn from two clinical trials, PEAR and GERA - analyzed this variant; that study's primary genome-wide significant finding for triglyceride response in African Americans was in the NELL1 gene region (rs12279250 and rs4319515, r2=0.73), where each variant allele was associated with a 28 mg/dL increase in triglyceride change. Specific effect size and significance level for rs11810574 itself are not reported in the available study excerpt.

Reported associations

  • FMN2 expression in cultured fibroblasts: The ALT allele is associated with reduced FMN2 expression (slope -0.33, p=7.5e-6) in GTEx v11 data from 953 donors GTEx Portal.
  • HCTZ-induced metabolic effects (African Americans): This variant was analyzed in a GWAS of changes in fasting plasma glucose and triglycerides following HCTZ treatment in African American hypertensive patients; specific effect size and significance level for rs11810574 are not reported in the available study excerpt.

Evidence quality The eQTL association from GTEx v11 is based on 953 donors with a false discovery rate below 0.05, representing the most quantitatively described finding for this variant GTEx Portal. The GWAS providing HCTZ context draws from two clinical trials (PEAR and GERA) enrolling adults with mild-to-moderate primary hypertension and focuses on African American participants. However, specific statistical results for rs11810574 are not detailed in the available study text, and the study's primary genome-wide significant locus was NELL1. No independent replication of an rs11810574 association is present in the provided studies. Evidence for this variant should be considered preliminary.

Tissue-specific expression effects

  • FMN2: The ALT allele is associated with reduced expression in cultured fibroblasts; this is the only tissue reaching GTEx v11 significance (FDR<0.05) for this eQTL in the provided data GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the FMN2 gene?

FMN2 is a gene whose expression levels were measured in large-scale genetic datasets. Carriers of the ALT allele at rs11810574 show lower FMN2 activity in fibroblast cells, though the studies reviewed do not describe FMN2's specific biological function.

What does rs11810574 have to do with blood pressure medication?

This variant appears in a genome-wide association study that investigated why some patients experience elevated blood sugar or triglycerides after taking hydrochlorothiazide (HCTZ), a widely used diuretic prescribed for high blood pressure. HCTZ is among the most commonly prescribed antihypertensive medications, with over 110 million annual prescriptions in the United States.

How strong is the evidence for rs11810574?

Evidence is preliminary. The eQTL finding from GTEx v11 (953 donors, FDR<0.05) is the best-supported result. The GWAS placing this variant in the context of HCTZ side effects does not report specific effect sizes for rs11810574 in the available study text, and no independent replication data is provided.

What is an eQTL and why does it matter here?

An eQTL (expression quantitative trait locus) is a genetic variant associated with differences in how much a gene is expressed. For rs11810574, the ALT allele is linked to lower FMN2 expression in fibroblast cells, which may hint at a biological mechanism but does not by itself predict any health outcome.

What populations were studied in the HCTZ GWAS?

The GWAS drew from two clinical trials - PEAR and GERA - enrolling adults with mild-to-moderate primary hypertension. The reported genome-wide significant findings focused on African American participants.