rs11187837 (PLCE1): Cardiac Arrest & Gene Expression

Key takeaways

• This variant has opposite effects on PLCE1 gene activity in different tissues, increasing expression in immune cells but reducing it in thyroid.
• A small pilot study examined this region in connection with sudden cardiac arrest risk in coronary artery disease, but findings need replication in larger cohorts.
• The variant also reduces activity of PLCE1-AS1, a nearby regulatory RNA, in visceral fat tissue and skin cells.
• A neighboring gene, NOC3L, shows higher activity in skeletal muscle but lower activity in thyroid tissue in carriers of this variant.

What the research says A pilot genome-wide association study (GWAS) typed 338,328 tagging SNPs across the genome in 89 Caucasian non-Hispanic patients with coronary artery disease (CAD) who had aborted sudden cardiac arrest (SCA) due to documented ventricular tachycardia (an abnormally fast heart rhythm) or ventricular fibrillation (chaotic electrical activity in the heart), comparing them to 520 healthy controls; the authors explicitly state that validation in independent cohorts and functional studies are required before any associations can be considered confirmed. The variant rs11187837 falls in the PLCE1 locus - phospholipase C epsilon 1, an enzyme that transmits chemical signals inside cells - and eQTL (expression quantitative trait locus) data from GTEx v11 (953 donors, FDR < 0.05) shows that this variant drives significant, tissue-specific changes in expression of PLCE1 and two neighboring transcripts GTEx Portal. Notably, the PLCE1 eQTL effect runs in opposite directions across tissues: strongly increased expression in EBV-transformed lymphocytes (a laboratory cell-line model of B-cell immune function; slope +0.84, p = 6.4 × 10^-²²) versus modestly reduced expression in thyroid tissue (slope −0.17, p = 5.1 × 10^-5) GTEx Portal.

Reported associations

• Sudden cardiac arrest in coronary artery disease patients: A pilot GWAS (89 SCA cases with documented ventricular tachycardia or fibrillation and a history of myocardial infarction; 520 healthy controls; 338,328 SNPs typed genome-wide) examined genetic variation in this genomic region; the study describes all findings as preliminary and requiring independent replication and functional validation before conclusions can be drawn.
• PLCE1 expression - EBV-transformed lymphocytes: The alternate allele is associated with substantially increased PLCE1 expression (slope +0.84, p = 6.4 × 10^-²²) in EBV-transformed lymphocyte cell lines GTEx Portal.
• PLCE1 expression - thyroid: The alternate allele is associated with modestly reduced PLCE1 expression (slope −0.17, p = 5.1 × 10^-5) in thyroid tissue GTEx Portal.
• PLCE1-AS1 expression - visceral adipose tissue and cultured fibroblasts: The alternate allele is linked to reduced expression of PLCE1-AS1 (an antisense non-coding RNA - a regulatory molecule that does not produce a protein - at the same locus) in visceral omentum fat (slope −0.27, p = 1.1 × 10^-5) and cultured skin fibroblasts (slope −0.27, p = 4.8 × 10^-¹^0) GTEx Portal.
• NOC3L expression - skeletal muscle and thyroid: The alternate allele is associated with increased NOC3L expression in skeletal muscle (slope +0.16, p = 5.1 × 10^-5) and reduced NOC3L expression in thyroid tissue (slope −0.16, p = 6.3 × 10^-7) GTEx Portal.

Evidence quality The SCA GWAS is an explicitly pilot study: with 89 cases and 520 controls restricted to Caucasian non-Hispanic individuals, it is underpowered for definitive genetic discovery, and the authors themselves call for validation in independent cohorts and functional studies. The study applies Bonferroni correction (p < 1.30 × 10^-7) and adjusts for population substructure, age, and sex, but no replication data are presented, and a statistically significant direct association between rs11187837 specifically and SCA is not enumerated in the available study text - the locus is included here because the GWAS was provided in this variant's context. The GTEx eQTL evidence carries higher methodological confidence, drawn from 953 donors at FDR < 0.05, but it describes regulatory relationships rather than clinical outcomes; the biological and health consequences of altered PLCE1, PLCE1-AS1, or NOC3L expression have not been established by functional research. The opposite PLCE1 eQTL direction in lymphocytes versus thyroid (increased versus decreased expression from the same allele) is a finding of note in itself: it demonstrates that this locus's regulatory effects are strongly tissue-specific and should not be generalized across organ systems.

Tissue-specific expression effects

• PLCE1: Increased expression in EBV-transformed lymphocytes (a B-cell line model of immune function) and reduced expression in thyroid tissue GTEx Portal.
• PLCE1-AS1: Reduced expression in visceral adipose tissue (omentum) and in cultured skin fibroblasts GTEx Portal.
• NOC3L: Increased expression in skeletal muscle and reduced expression in thyroid tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.