*3.2. Genetic Studies of KLF15 in Patients with LVH*

Conventional risk factors do not explain all the variability in LVH [23], and a heritable component underlying LVH is recognized. We recently explored the genetic association of *KLF15* single nucleotide polymorphisms (SNP) in patients with type 2 diabetes and an echocardiographic assessment of LV mass [2]. The intronic *KLF15* SNP rs9838915 A allele was significantly associated with LV mass and the association was replicated in an independent cohort of >5000 type 2 diabetes patients (Table 3). The *KLF15* rs9838915 A allele predicted the first hospitalization with heart failure [24]. No other genetic studies have been conducted in this area. Analysis of the GTEx data, [25], identified 84 expression quantitative trait loci downstream of *KLF15* as highly significant (*p* values 0.00011 to 3.810−8, false discovery rate <5%, alternative allele effect sizes from 0.12–0.16) modifiers of KLF15 gene expression in transformed fibroblasts. Although the rs9838915 SNP was not examined in GTEx, the data suggest that *KLF15* SNPs have the functional potential to influence KLF15 expression. Recently, Ferreira et al. [26] conducted a bioinformatics analysis focused on non-synonymous variants in KLF genes using algorithms to predict the effect of variants on the genes structure and function. Two *KLF15* intronic variants, one located in the conserved Zinc-finger domain and the other in a non-conserved

region was predicted to affect DNA binding or protein destabilization and hence may lead to disrupted KLF15 protein function. The frequency of these variants is <0.0001 in the population and therefore unlikely to contribute to LVH in the general population.


*↑* Increased; *↓* decreased. CABG, coronary artery bypass graft; mRNA, messenger ribonucleic acid; LV, left ventricle; LVAD, left ventricular assisted device; LVH, left ventricular hypertrophy; KLF15, Kruppel-like factor 15; SNP, single nucleotide polymorphism.
