Genetic variants and haplotype structures of miRNA host genes in cancer and obesity.

Abstract

Cancer and obesity are two important public health problems. This study aimed to investigate the role of genetic variants and haplotypes of miRNA host genes in cancer and obesity. Data from the catalog of genome-wide association studies (GWAS) were used to find significant variants (index). Then, 1000-genome phase 3 data were used to find haplotypic variants (proxy) associated with these diseases. The candidate variants and haplotypes were identified from proxy and index variants. Finally, SNP function analysis was performed. All GWAS-significant cancer-associated miRNA host gene variants, including MIR4713HG, MIR663AHG, MIR99AHG and MIR4435-2HG, were also significantly associated with obesity. The rs703764 variant was common between cutaneous melanoma and obesity traits in the European population (P ≤ 5E-8). The rs2414098 variant was associated with endometrial cancer (P ≤ 5E-13), and the rs7173595 variant was associated with waist-hip ratio (P ≤ 5E-13) and new CGGCATCA haplotypic located at MIR4713HG was identified in the European population. In addition, the ATCTTGTT haplotype for rs17041868 in MIR4435-2HG was identified to be associated with obesity traits (waist-hip ratio and BMI) in the European population (P ≤ 5E-8). This study found that rs703764 is a common genetic marker between cancer and obesity. The CGGCATCA haplotype is common between endometrial cancer and waist-hip ratio. Also, ATCTTGTT haplotype is associated with obesity traits. These results indicate that the variants and haplotypes of miRNAs host genes play an important role between cancer and obesity in the European population. It is suggested to investigate the effect of these structures in other populations.