Biological and clinical significance of haptoglobin polymorphism in humans

TLDR

Haptoglobin, a hemoglobin‑binding protein with three major phenotypes (1‑1, 2‑1, 2‑2), has been studied mainly as a forensic genetic fingerprint, but recent evidence indicates its involvement in immune responses and strong evolutionary pressure favoring the 2‑2 phenotype, underscoring its potential role in human pathology. These effects are explained by a phenotype‑dependent modulation of oxidative stress and prostaglandin synthesis. Functional differences among haptoglobin phenotypes have important biological and clinical consequences, and polymorphism is linked to the prevalence and progression of various inflammatory diseases such as infections, atherosclerosis, and autoimmune disorders.

Abstract

Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.