Mutation That Induces High Blood Pressure in Women Linked to Increased Heart Attack Risk

A mutation in women in the G-protein coupled estrogen receptor 30 (GPER) gene generates a receptor with reduced activity that induces high blood pressure, the single biggest risk factor for heart attack and stroke.

The GPER gene is a member of the G-protein coupled receptor 1 family and encodes an integral membrane protein with high affinity for estrogen that localizes to the endoplasmic reticulum. The protein binds estrogen, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen.

Investigators at the Schulich School of Medicine & Dentistry (London, ON, Canada) found that a common missense genetic variant of GPER, P16L GPER, was poorly functional when expressed in vascular smooth muscle cells. Furthermore, females—but not males—carrying this genetic variant had increased blood pressure and had a higher allelic prevalence in a highly selected population of hard-to-treat hypertensive patients.

"This is one step in understanding the effects of estrogen on heart disease, and understanding why some women are more prone to heart attack and stroke than others," said senior author Dr. Ross Feldman, professor of medicine and physiology/pharmacology at the Schulich School of Medicine & Dentistry. "Our work is a step forward in developing approaches to treating heart disease in this under-appreciated group of patients."

The study was published in the July 21, 2014, online edition of the British Journal of Clinical Pharmacology.

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