Haplotype analysis of carnitine transporters and left ventricular mass in human essential hypertension

Objective The carnitine-associated alteration of myocardial fatty acid metabolism may be one of the molecular mechanisms underlying left ventricular hypertrophy (LVH) in essential hypertension. We tested the hypothesis that polymorphisms of the genes involved in carnitine transport, OCTN2, CPT1A, CPT1B, and CPT2, might be associated with LVH. Design Haplotype-based association analysis in an observational study. Setting Outpatients from the Nephrology Division of the University Hospital. Patients A total of 215 never-treated, middle-aged patients with mild essential hypertension. Methods Relationships between left ventricular mass index (LVMI) (measured with m-mode echocardiography) and haplotype combinations for 13 common genetic variants selected from single nucleotide polymorphism database (dbSNPs). Results The SNPs were selected to cover the genomic region of the four loci, and a total of 23 haplotypes were identified: 8 for OCTN2 (H1 to H8), 8 for CPT1A (H9 to H16), 3 for CPT1B (H17 to H19), and 4 for CPT2 (H20 to H23). In a multilocus haplotype analysis, after adjusting for sex, age, systolic blood pressure, diastolic blood pressure, body mass index, and duration of hypertension, a significant effect on LVMI was seen for H13 (+8.9, P = .05), H14 (−5.63, P = .05), H15 (−18.79, P = .0006), H18 (−1.66, P = .03), and H22 (−3.42, P = .004). These significant haplotypes were respectively 3.7%, 1.6%, 1.6%, 39.3%, and 29.7% of the total population. Conclusions These results identify the carnitine-transporter gene family as candidate modifiers of LVMI in human hypertension. The use of common SNPs to define informative haplotypes associated with the phenotype of interest is the starting point for progress toward identification of the trapped contributing SNP(s).