Common variation neighbouring micro-RNA 22 is associated with increased left ventricular mass

Abstract

Aims: Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22), has been implicated in cardiac hypertrophy and heart failure in animal models. We thus investigated the relationship between common genetic polymorphisms surrounding miR-22 and left ventricular mass in a family-based association study.

Methods and results: We studied a cohort of 255 families comprising 1,425 individuals ascertained via a hypertensive proband. Ten single nucleotide polymorphisms which together tagged common genetic variation surrounding the miR-22 gene were genotyped. There was evidence of association between the rs7223247 polymorphism, which lies within the 3'UTR of a gene of unknown function, TLCD2, immediately downstream from miR-22, and left ventricular mass determined by Sokolow-Lyon voltage (Bonferroni corrected p-value = 0.038). The T allele at rs7223247 was associated with an 0.272 standard deviation higher Sokolow-Lyon voltage. Genotype was responsible for ~1% of the population variability in LVM.

Conclusions: Genotype at the rs7223247 polymorphism affects left ventricular mass determined by Sokolow-Lyon voltage. The neighbouring genes miR-22 and TLCD2 are strong candidates to account for this observation.

Figure 1. SNPs at the miR-22 locus.

All SNP locations are indicated by lines on the miR-22 schematic (17p13.3/30.0 kb) derived from the UCSC genome browser (http://www.genome.ucsc.edu/). The Haploview output is directly related to the schematic, with the linkage disequilibrium relationships between HapMap Phase 3 SNPs in the region shown, indicating the three principal haplotype blocks. Darker squares represent higher R-squared between markers. rs7223247 is circled in red. SNPs chosen for genotyping (at threshold MAF = 0.05, r² = 0.8) are enclosed within green boxes.