Men tend to get coronary artery disease much earlier than do women. For some men, the reason for that might be in part because of their fathers—and their father's father—according to a new study, published online Wednesday in The Lancet.
The study analyzed data from 3,233 unrelated white men enrolled in previous U.K. studies. From this information, the researchers took a close look at genetic markers on the Y chromosome, which is passed on from father to son. They found that 15 to 20 percent of the men fell into one of the 13 ancient ancestry branches known as haplogroup I.
Men in this haplogroup, who all showed a common variant on the Y chromosome, were 50 percent more likely to have coronary artery disease than those without it—even when age, body mass, cholesterol, high blood pressure, smoking and other risk factors were taken into account. The genetic link is not entirely surprising, given that heart disease has been known to run in families, but the finding adds support to previously observed trends—and insights into additional lines of research.
The finding follows well-described geographic distribution of coronary artery disease. Haplogroup I has been traced back to hunter-gatherers who arrived in Europe from the Middle East some 25,000 years ago and who today remain more prevalent in the northern areas of western Europe, where incidence of coronary artery disease is still higher than it is in the south—where the haplogroup R1b1b2 is more common.
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. "Dysfunction of immune response is a well established contributor to atherosclerosis and coronary artery disease," they wrote. Previous research had found other immuno differences in men from this haplotype, such as HIV-positive men in this group taking longer to show an immune response after getting antiretroviral therapy.
The findings do not suggest that heart disease risk for men is entirely—or even mostly—lodged on the Y chromosome. And the researchers noted that knowing which haplogroup a man is from is unlikely to yield predictions of his individual risk of coronary artery disease. But, as they pointed out, a better understanding of this widespread association "could have important public health implications," especially in attempts to assess the prevalence of the disease within a population. And further study should help "to decipher complex interplay between human Y chromosome, immunity and cardiovascular disease," the researchers wrote.
"These findings are exciting," Virginia Miller of the Mayo Clinic wrote in an associated Lancet essay (Miller was not involved in the new research). The new work also suggests that there could be another side to the genetic equation that is protective, she added.