A recent study published by The Lancet suggests that males with a certain variant on their Y-chromosome are at a 50% higher risk of developing coronary artery disease (CAD). The study, led by Dr Maciej Tomaszewski, Department of Cardiovascular Sciences, University of Leicester, UK and Dr Fadi J Charchar, University of Ballarat, Australia, provides insight into the roles that Y-chromosomes have in health and disease.
The Y-chromosome is exclusively found in men – passed on from father to son – and is responsible for maleness and fertility. For many years it had been unclear what other roles the chromosome may have in health and disease.
A total of 3233 British men -biologically unrelated- were included in three panel studies: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. The researchers determined differences in the genetic makeup of 11 markers of the male-specific region of the Y chromosome. Using this information they were able to track back the men’s chromosomes to one of 13 ancient lineages defined as haplogroups.
The results found that around 15-20% of the British male population are carriers of haplogroup I, men carrying this chromosome variant were found to have a 50% higher age-adjusted risk of CAD compared to those carrying other Y chromosome lineages in the BHF-FHS and WOSCOPS.
Researchers revealed that the haplogroup I variant causes a downregulation of adaptive immunity and upregulation of inflammatory response pathways in macrophages, thus increasing the risk of developing CAD. The authors note that male predisposition to CAD could be directly related to the paternal lineage of their Y chromosome.
The authors say:
“Our study is the first to evaluate associations between main European Y chromosome lineages and CAD as well as its underlying risk factors…[it has] revealed that the Y chromosome might have a magnified effect on men beyond sex determination despite the small number of genes it harbours in the human genome.
Future resequencing efforts and functional experiments will be needed to identify the causative variants underlying the increased susceptibility to coronary artery disease in carriers of haplogroup I and to decipher complex interplay between human Y chromosome, immunity, and cardiovascular disease.”
Dr Virginia Miller, Mayo Clinic, Rochester, MN, USA, comments:
“Avenues for future research should include exploration of potential interconnections among pathways relating immunity to other forms of cardiovascular disease, such as those identified for various cardiomyopathies.
Finally, it would be interesting to examine whether existing algorithms assessing individual risk of coronary artery disease for men could be improved by changing the question ‘Did your mother or father have a heart attack before age 60?’ to ‘Did your father have a heart attack before the age of 60?’ Both sex and family do matter in inheritance of coronary artery disease.”
Written by Joseph Nordqvist