Among men of European ancestry, a variant on the Y
chromosome is associated with a 50% higher risk for coronary artery disease,
likely caused by interactions of immunity and inflammation, according to recent
study data.
The researchers genotyped 11 male-specific markers of
the Y chromosome in 3,233 biologically unrelated men from three cohorts:
BHF-FHS, WOSCOPS and Cardiogenics study. By examining this information, they
traced each Y chromosome back to one of 13 ancient lineages, defined as
haplogroups. Of nine haplogroups identified, researchers found two —
R1b1b2 and I — that accounted for approximately 90% of Y chromosome
variants among British men.
Men with haplogroups I, approximately 15% to 20% of
British men, had about a 50% higher age-adjusted risk for CAD vs. men with
other Y chromosome lineages in BHF-FHS (OR=1.75; 95% CI, 1.2-2.54), WOSCOPS
(OR=1.45; 95% CI, 1.08-1.95) and a joint analysis of both populations
(OR=1.56-; 95% CI, 1.24-1.97), according to study results. Researchers found
men with CAD in the BHF-FHS cohort were more likely to have haplogroup I (20%)
vs. controls without CAD (13%; P=.0001). Similarly, haplogroup I was
more common in men who developed CAD during 4.9 years (18%) vs. controls (13%;
P=.014) in the WOSCOPS cohort. Adjustment for socioeconomic and
traditional CV variables did not weaken the association of haplogroup I with
CAD (OR=1.60; 95% CI, 1.16-2.19). Study results showed that haplogroup I was
the most significant prediction of CAD after HDL and lipid-lowering treatment.
In a functional analysis of macrophage transcriptome in
the Cardiogenics study, researchers found that 19 molecular pathways showing
strong differential expression between men with haplogroup I and other lineages
of the Y chromosome were interconnected by common genes related to inflammation
and immunity, suggesting that some of these pathways may affect the development
of atherosclerosis.
In an accompanying editorial, Virginia Miller,
PhD, of the department of surgery and physiology at the Mayo Clinic, wrote:
“These findings are exciting because they identify a genetic haplotype
linking response to infection — adaptive immunity — rather than
innate immunity with perhaps an exaggerated inflammatory response and CVD in
men.”
According to Miller, when it comes to inheritance of
CAD, both sex and family matter. She said future research should include
interconnections of pathways relating immunity to other forms of CVD and
whether comparable genes in the X chromosome are susceptible to autoimmune
disorders.
For more information:
Disclosure: The researchers report no relevant
financial disclosures. Dr. Miller reports no relevant financial disclosures.