Fathers may pass on heart disease risk to their sons finds a new study.
The study, published in The Lancet, focused on genetic markers on the Y chromosome — which is present only in male DNA (women have two X chromosomes) — and found that men with a certain genetic variant were 50% more likely to have coronary artery disease than those without it. The increased risk was independent of other contributors to heart disease such as age, weight, high cholesterol, high blood pressure and smoking.
The haploid Y chromosome contains the smallest number of genes. The main part of the Y chromosome is transmitted intact from father to son, and contains single and multi-copy genes that encode about 27 distinct proteins. The biological role of the Y chromosome is to impart male characteristics.
Using genetic information on the Y chromosome, an international team of researchers identified 9 different ancient lineages– haplogroups– in 3,233 British men. Two of the haplogroups accounted for nearly 90% of the subjects and men in one of these haplogroups, haplogroup I, had a 50% increase in the risk of coronary artery disease compared to men with other haplotypes. This increase in risk was independent of other known risk factors. The investigators noted that haplogroup I appeared to exert a powerful effect on genes relating to inflammation and immunity. They further noted that haplotype I is generally more prevalent in northern than in southern Europe, and that this distribution is paralleled by an increased risk of coronary artery disease in northern Europe.
The genetic variant came with altered patterns of regulation in 19 key pathways — all of which were linked to immune and inflammatory responses. These differences might play a role in atherosclerosis, or the hardening of the arteries, noted the researchers, who were led by Fadi Charchar, of Australia’s University of Ballarat.
The study is exciting for researchers because it gives the role of the Y chromosome new meaning. “The major novelty of these findings is that the human Y chromosome appears to play a role in the cardiovascular system beyond its traditionally perceived determination of male sex,” said principal investigator Dr. Maciej Tomaszewski, a clinical senior lecturer in the University of Leicester department of cardiovascular sciences, in a statement.
Authors concluded, “Our study is the first to evaluate associations between main 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 harbors in the human genome.”
The authors, however, added that future re-sequencing and functional experiments will be needed to identify the causative variants underlying the increased susceptibility to CAD in carriers of haplogroup I and to decipher complex interplay among human Y chromosome, immunity and cardiovascular disease.
Overall, men get heart disease 10 to 15 years earlier and twice as often as women. After menopause, however, women’s risk of heart disease is closer to that of men, and heart disease is the leading killer of both men and women.
Dr Virginia Miller, Mayo Clinic, says, “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 matter in inheritance of coronary artery disease.”
Dr. Daniel J. Rader, a heart disease researcher at the University of Pennsylvania, said it was also possible that simply having a Y chromosome instead of two X chromosomes, as women have, increased heart disease risk. The extra X could be protective.
Dr. Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, said it was strange that there had been almost no study of the Y chromosome’s effect on heart disease. Although the reasons were technical, having to do with the way gene searches were done, ignoring the Y, he said, “was a little bit of an oversight.” Dr Kathiresan said the association between the gene cluster and heart disease risk needed to be confirmed.