Evaluation of the relationship between UMOD gene variants and cardiovascular complications among children with hypertension

Hypertension is one of the biggest public health problems in the world. With the increasing frequency of obesity, this problem is more evident in children. While in the past, the most common type of hypertension in children was secondary to renovascular disease, today, we see primary hypertension as the most common type because of the increasing prevalence of obesity. Specific renal, endocrine, vascular, and other mechanisms play a regulatory role in maintaining blood pressure, and each of those mechanisms is regulated by multiple genes. Identifying variants in these genes is essential in terms of followup and treatment for hypertensive pediatric patients. Over 500 single nucleotide polymorphisms associated with blood pressure and hypertension are already discovered. Numerous studies on adult patients show that the strongest linked ones are UMOD gene variants. Despite the lack of studies that include pediatric patients, adult studies show UMOD gene variants closely related to chronic kidney disease and hypertension. UMOD gene variant frequency was found to be 80%. These mutations increase the risk of chronic kidney diseases by 20% and hypertension by 15%. In light of this information, we evaluated the relationship between cardiovascular complications and three mutations located in the UMOD promoter region showing strong evidence of an increase in the risk of hypertension which were; rs4293393(UMOD42), rs13333226(UMOD13), and rs11864909(PDILT). At the same time, descriptive analyses were performed on our patient population. The prevalence of increased blood pressure in our population was 69.7% for males and 30.3% for females. The prevalence of obesity in the case group was 26.7%. When divided by the etiology, 68% had primary hypertension, 22.9% had hypertension secondary to renovascular disease, and 9.1% had hypertension secondary to other causes. On detailed cardiac examination of 66 patients, 37 had diastolic dysfunction 16 of which did not have any evidence of left ventricular hypertrophy or systolic dysfunction. 20 (54%) of these 37 patients had a substitution mutation on at least one allele of the before-mentioned genes. We concluded that the follow-up of hypertensive patients with M-mode echocardiographic imaging performed during routine outpatient clinic visits would be insufficient. Instead, these patients should be evaluated using tissue Doppler to detect diastolic dysfunction, an earlier marker for cardiac involvement. 59 Since conventional echocardiography is used for the routine follow-up of these patients, early diastolic dysfunction might be overlooked, which may be irreversible in terms of cardiac complications. Our study again showed the importance of using tissue doppler to investigate these patients' diastolic cardiac functions. Our study did not find a statistically significant correlation between UMOD gene variants and left ventricular hypertrophy in the case group. Since our study is the first to examine the relationship between genetics of hypertension and cardiovascular complications in pediatric population, it should be supported by studies involving larger patient groups.