Variability gene effect on cholesterol at the Kidd blood group locus.

The within-pair difference in lipid levels was examined in 142 monozygotic (MZ) twin pairs drawn from the population-based Norwegian Twin Panel. Mean within-pair difference in serum total cholesterol was lower in MZ pairs who were heterozygous for blood group Kidd genes or homozygous for the Jkb gene than in pairs who were homozygous for the Jka gene. The difference between the two categories of homozygotes was significant at the 2% level. The analyses suggest that the main reason for the difference observed is a restrictive effect of the Jkb gene on total cholesterol variability. No effect on triglycerides or HDL cholesterol variability was detected and there was no association between Kidd blood groups and sex and age-adjusted levels of cholesterol, triglycerides or HDL cholesterol. The present data confirm findings we reported when we introduced the study of within-pair variability in MZ twins as a method to analyze gene-environment interactions and validate the "variability gene" concept. A person's net risk for coronary heart disease may depend on his or her combination of "level genes" and "variability genes" as well as on environmental or life-style factors.