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Heart disease risk passed from father to son

Adrian O'Dowd

Thursday, 9 February 2012

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Men are 50% more likely to develop coronary artery disease if they have a common variant of their Y chromosome inherited from their father, claims a study published online today in The Lancet.

The Y chromosome, exclusive to men, is inherited from fathers to sons and apart from determining maleness and fertility, the other roles of the chromosome in health and disease have been unclear so far.

Men develop coronary artery disease approximately 10 years earlier than women so researchers set out to investigate the role of the Y chromosome in this disease.

The international study of 3,233 men was led by a team of researchers from the University of Leicester.

The researchers genotyped 11 markers of the male-specific region of the Y chromosome in 3,233 British men who were part of three ongoing studies into heart disease – the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study.

Using this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups.

The researchers found that 90% of the men had one of two common versions of Y chromosome – haplogroup 1 and haplogroup R1b1b2 – and the risk of coronary heart disease was 50% higher in men who had the haplogroup 1 version than in other men with other Y chromosome lineages.

Overall, 15-20% of British men are estimated to have the haplogroup 1 version of Y chromosome.

The link between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors, such as age, body-mass index, blood pressure, lipids, diabetes, smoking, alcohol consumption, or socioeconomic status.

Further analysis showed that men with haplogroup I were likely to experience a weaker immune system.

The authors conclude: “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.”

The British Heart Foundation, which partially funded the study, said the research added useful knowledge to the fight against heart disease.

The charity’s research advisor Dr Hélène Wilson said: “Coronary heart disease is the cause of heart attacks, which claim the lives of around 50,000 UK men every year.

“Lifestyle choices such as poor diet and smoking are major causes, but inherited factors carried in DNA are also part of the picture. The next step is to identify specifically which genes are responsible and how they might increase heart attack risk.

“This discovery could help lead to new treatments for heart disease in men, or tests that could tell men if they are at particularly high risk of a heart attack.”

DOI:10.1016/S0140-6736(11)61453-0

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