Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease

Most studies aiming to detect associations of genetic variation with common complex diseases, e.g. coronary heart disease (CHD) have been performed in populations with a western lifestyle but it is unclear whether associations detected in one geographic group exist also in others. We here have determined lipoprotein(a) levels and apo(a) K-IV-2 repeat genotypes in CHD patients (N=254) and controls (N=480) from two Asian Indian populations (Tamil Nadu and New Delhi). In both populations and also in the pooled dataset median Lp(a) levels were significantly elevated in the patients (27.4 mg/dl) compared with the controls (17.6 mg/dl). Apo(a) K-IV-2 allele frequencies were not different between the CHD patients and controls and thus did not explain the increased Lp(a) levels in CHD patients. Contrary to what has recently been observed in Black and White men short (K-IVor=22) alleles associated with high Lp(a) concentration were not overrepresented in the patients. Rather, short (K-IVor=22), intermediate (K-IV 23-29) and long (K-IVor=30) apo(a) alleles were all associated with higher Lp(a) levels in the patients. Accordingly relative risk (estimated as odds ratio) for CHD rose continuously with increasing Lp(a) but was independent of apo(a) allele length. Together with previous studies our results indicate that the relation between apo(a) genotypes, Lp(a) levels, and CHD may be heterogeneous across ethnic groups and that it depends on the genetic architecture of the Lp(a) trait in a given population whether an association of K-IV-2 repeat length with CHD exists or not.