Genetics of systemic sclerosis-associated pulmonary arterial hypertension: Recent progress and current concepts

Abstract

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Although there are screening tests for PAH, such as carbon monoxide diffusing capacity and Doppler echocardiography, these tests are far from perfect, patients are still identified late in the course of disease, and the underlying mechanisms of SSc-associated PAH are poorly understood. Understanding the genetic differences between those patients with SSc who do and do not develop PAH may improve our ability to identify and treat patients earlier in the course of disease. To date, only a few candidate gene association studies and one gene expression analysis have investigated the genetics of PAH in SSc. These studies highlight the important opportunities and challenges for exploration of genetics of complex traits. By appreciating the optimal conduct of genetic studies, along with the role of bioinformatics resources such as the International HapMap database, investigators and clinicians will be better equipped to understand the genetics of SSc-associated PAH.

Association of a KCNA5 gene polymorphism with systemic sclerosis–associated pulmonary arterial hypertension in the European Caucasian population

“…SSc is also a complex disorder in which multiple susceptibility genetic factors predispose certain individuals to disease subphenotypes. Several studies have attempted to identify genetic risk factors for PAH associated with SSc, but despite some relevant preliminary results, a lack of appropriate cohorts (because of imperfect phenotype and/or insufficient statistical power) has precluded definite conclusions (25).…”

Review: Evidence That Systemic Sclerosis Is a Vascular Disease

“…These findings provide the rationale for the current vasodilator therapy used to treat patients with SSc‐related PAH. While potential common molecular pathways for pulmonary vascular disease have been regularly discovered (), knowledge of genes marking susceptibility to the disease is only just emerging (). Recently, the first evidence for an association of the KCNA5 single‐nucleotide polymorphism rs10744676 with SSc‐associated PAH was reported ().…”