Nature Medicine | Spoonful of Medicine

Gene associations galore

This week’s issue of JAMA struck me as pretty interesting. They normally publish stuff that’s too clinical or epidemiological for my taste and in comparison to what we publish, but this time they had a themed issue on genomics with four articles reporting associations between gene variants and diseases of different systems.

Two of the articles are relevant to the cardiovascular system. First, Tamali Bhattacharyya and colleagues established a link between polymorphisms that affect the function of paraoxonase 1 (an HDL-bound enzyme with cardioprotective properties), oxidative stress and cardiovascular disease. As might be expected, forms of the enzyme with higher activity were associated with less oxidative stress and a reduced risk of cardiac events.

The second paper, by Irene Bezemer and her colleagues, disclosed gene polymorphisms linked to deep vein thrombosis. These variants affected several genes (CYP4V2, SERPINC1, GP6, KLKB1 and F11), and some of these were also linked to higher levels of coagulation factor XI, hinting at a possible molecular mechanism.

Next, a study by Joyce van Meurs and colleagues reports polymorphisms in the low-density lipoprotein receptor-related protein LRP5 that are associated with osteoporosis. As mutations in LRP5 had already been linked to bone disorders, it is not entirely surprising that variants of this gene would lead to reduced bone density and increased fracture risk.

Last, but not least, there’s a very intriguing contribution by Elisabeth Binder and her colleagues, who found that variants in the FKBP5 gene (which encodes a protein that interacts with the glucocorticoid receptor to modulate its cortisol-binding affinity and has therefore been linked to physiological responses to stress) interact with the occurrence of abuse during childhood, predicting the severity of posttraumatic stress disorder (PTSD) in adulthood. The gene variants themselves were not good predictors of PTSD. So, this is a fine example of gene-environment interactions in the context of mental disease.

Very interesting associations indeed. Hopefully they’ll lead to some hardcore molecular work that results in some mechanistic insight into the biological meaning of this gene polymorphisms that goes above and beyond the correlations found in these studies.

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