Association of Rho/Rho-kinase gene polymorphisms and expressions with obesity-related metabolic syndrome

The metabolic syndrome (MetS) is a common multicomponent condition including abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The aim of this study was to investigate the associations of Rho GTPase and Rho-kinase (ROCK) gene polymorphisms and expressions with MetS in a Turkish population.

A total of 141 obese MetS patients and 163 healthy controls with similar age and sex were included to this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions.

We observed that genotype (CC, 18.1%; CA, 13.4%, and AA, 68.5%) and allele (C, 24.8%; A, 75.2%) frequencies for the rs35996865 polymorphism of the ROCK1 gene in patients were markedly different from controls (CC, 84.2%; CA, 2.9%, and AA, 12.9%; C, 85.6%; A, 14.4%, p < 0.0001). In the rs2230774 (Thr431Asn) polymorphism of the ROCK2 gene, there were increases in the CC genotype (16.5%) and C allele frequencies (20.4%) in MetS patients when compared with the control group (CC, 6.0%, p = 0.0009, and C, 6.7%, p < 0.0001). However, no associations with the other 18 polymorphisms studied were found. Although there were an increase in peripheral blood mRNA RhoH expressions, marked decreases in RhoC, RhoBTB1, RhoV, Rnd1, and CDC42 gene expressions were noted in MetS patients.

This is the first study to provide evidence that ROCK gene polymorphisms and gene expressions of the Rho GTPase proteins may modify individual susceptibility to MetS in the Turkish population.