Genetic Polymorphism Associated with Increased Cardiovascular Mortality

The platelet-derived growth factor (PDGF) family performs a multitude of functions such as vasodilation, regulation of erythropoiesis, and wound repair, but are also major mitogens for fibroblasts and smooth muscle cells, and are involved in the atherosclerotic process in the body.

The PDGF family presently consists of four members, PDGF-A, PDGF-B, and the recently discovered PDGF-C and PDGF-D. After a myocardial infarction, increased levels of PDGF-D in the infarcted tissue have been reported, a fact that has been interpreted to indicate involvement of PDGF-D in the repair process.


Scientists at the University Hospital of Linköping (Sweden) enrolled 476 elderly community participants to be included in a study and they agreed to deliver blood samples, and could present Doppler-echocardiographic examinations with acceptable quality. All participants underwent a clinical examination, ECG recording, and Doppler-echocardiography, and blood samples were collected.

N-terminal pro b-type natriuretic peptide (NT-proBNP) was measured in the Elecsys 2010 platform (Roche Diagnostics, Mannheim, Germany). The total coefficient of variation (CV) for 70 participants was 4.8 % at 26 pmol/L and 2.1 % at 503 pmol/L at their laboratory. Genomic DNA was isolated from peripheral blood using the QIAmp DNA Mini Kit (QIAGEN, Hilden, Germany). A LightSNiP genotyping assay (TIB Molbiol GmbH, Berlin, Germany) was used for analysis of PDGF-D (rs974819) genotypes. DNA was and amplified using the Roche Diagnostics’ LightCycler 480 Real-Time PCR System.

The investigators found that no specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors and a 2.7 fold increased risk compared with the G/G genotype. No corresponding finding was observed in the female group.

The authors concluded that for the first time the genotypes G/A or A/A of the single nuclear polymorphism (SNP) rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. The present study has, however, applied an unusually long follow-up time to evaluate the end-result of the coronary heart disease process, and by applying a perspective over more than six years it might be possible to identify possible differences in risk also in this relatively small population. This might result in that more males are identified compared to females. The study was published on September 1, 2016, in the journal BMC Medical Genetics.

Related Links:
University Hospital of Linköping
Roche Diagnostics
QIAGEN
TIB Molbiol