Genetic risk scores in young hypertensive patients: implications for management and prevention across BMI categories

Abstract

The aim of the study was to analyze the proportion of modified candidate genes (CG) in young hypertensive patients (YHP) with normal weight, overweight, or obesity compared with non-hypertensive individuals, using the gene modification index (GMI) to evaluate the potential role of genetic stratification in the management of YHP.

Methods

A total of 123 YHP (mean age 32.8 years [18–44], male/female 72/51) and 30 non-hypertensive controls (mean age 31.1 years [18–44], male/female 17/13) were examined. YHP were divided into three groups according to BMI: Group 1: normal BMI (n = 41; BMI 23.0 ± 0.2 kg/m²), Group 2: overweight (n = 40; BMI 27.5 ± 0.2 kg/m²),Group 3: obesity (n = 42; BMI 34.3 ± 0.4 kg/m²) Genotyping of nine CG polymorphisms (ADD1:1378, AGT:704, AGT:521, AGTR1:1166, AGTR2:1675, CYP11B2:-344, GNB3:825, NOS3:-786, NOS3:894) was performed using PCR. The GMI reflected the percentage of “pathological” genotypes and was categorized as follows: 0–20%: low genetic risk (GR), 21–40%: moderate GR, 41–70%: high GR, 71–100%: very high GR

Results

The mean GMI was 45.3 ± 2.1% in Group 1, 56.4 ± 2.3% in Group 2, and 63.3 ± 2.4% in Group 3. Significant differences were observed between Group 1 and Groups 2 and 3 (p₁ = 0.031; p₂ = 0.004), while the difference between Groups 2 and 3 approached significance (p₃ = 0.053). GMI was significantly higher in overweight and obese hypertensive patients compared with those of normal weight. Analysis of individual CG polymorphisms revealed highly significant differences across the main groups (P₁,₂,₃ = 0.000).

Low GR was found in 14.6% of Group 1, 7.5% of Group 2, 2.4% of Group 3, and 83.3% of controls (p₁ = 0.121; p₂ = 0.026; p₃ = 0.194). Comparison with the control group showed highly significant differences for all groups (P₁,₂,₃ = 0.000). Moderate GR was observed in 31.7%, 22.5%, and 19% of Groups 1, 2, and 3, respectively, with no significant differences between groups (p₁ = 0.27; p₂ = 0.095; p₃ = 0.345); in controls, moderate GR occurred in 16.7%. High GR predominated in all YHP groups—34.2% in Group 1, 45% in Group 2, and 47.6% in Group 3—with no significant intergroup differences (p₁ = 0.13; p₂ = 0.088; p₃ = 0.43). Very high GR was also more frequent in overweight and obese YHP, though without statistically significant differences.

Conclusions

Young hypertensive patients demonstrated significantly higher GMI values compared with healthy young individuals, supporting the use of this index in pre-nosological diagnostics. Among YHP, the presence of overweight and especially obesity was associated with a markedly greater accumulation of modified CG polymorphisms. Integrative assessment of genetic cardiovascular risk using GMI represents a promising tool for the management, prognosis, and prevention of arterial hypertension in young adults.