J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 000, Number 000, July 2024, pages 000-000

Renin-Angiotensin System Genes Polymorphisms in Patients With COVID-19 and Its Relation to Severe Cases of SARS-CoV-2 Infection

**Table 1.** Main Clinical and Demographic Characteristics of Patients With COVID-19
	Total group (n = 100)	Severe course (n = 44)	Moderate course (n = 56)	Р value
P values for the group of severe vs. moderate COVID-19. CHD: coronary heart disease; CHF: chronic heart failure; CKD: chronic kidney disease; CRP: C-reactive protein; CT: computed tomography; DBP: diastolic blood pressure; GFR: glomerular filtration rate; HR: heart rate; LDL-C: low-density lipoprotein-cholesterol; RR: respiratory rate; SBP: systolic blood pressure; SpO₂: average value of oxygen saturation measured with a pulse oximeter; TG: triglycerides.
Age, years	58.5 (50.5 - 69.0)	59.5 (49.5 - 70.0)	56.5 (51.5 - 68.0)	0.409
Male gender, n (%)	49 (49)	21 (47.7)	28 (50)	0.778
Smoking, n (%)	13 (13)	5 (11.4)	8 (14.3)	0.522
SBP, mm Hg	125 (120 - 134)	129.5 (120 - 134.5)	125 (120 - 132)	0.661
DBP, mm Hg	80 (74 - 84)	80 (74.5 - 85)	80 (75 - 84)	0.883
HR, beats/min	80 (75 - 88.5)	84 (78.5 - 90.0)	80.0 (74.0 - 88.0)	0.154
BMI, kg/m²	28.74 (24.84 - 32.49)	30.04 (26.22 - 32.87)	27.66 (24.64 - 31.62)	0.129
RR, /min	22 (21 - 23.5)	23 (22 - 24)	22 (21 - 22)	0.0004
SpO₂, %	94 (92 - 96)	92 (91 - 93)	96 (95 - 97)	< 0.0001
Glucose, mmol/L	6.11 (5.69 - 6.7)	6.22 (5.81 - 7.05)	6.07 (5.55 - 6.48)	0.105
TG, mmol/L	1.62 (1.15 - 2.22)	1.71 (1.21 - 2.53)	1.61 (1.11 - 2.09)	0.316
LDL-C, mmol/L	2.94 (2.37 - 3.84)	2.80 (2.19 - 3.87)	3.03 (2.57 - 3.70)	0.282
GFR, mL/min/1.73 m²	75.8 (64.5 - 84.6)	78.4 (62.95 - 86.1)	73.6 (65.0 - 82.5)	0.483
CRP, mg/L	19.8 (7.0 - 50.55)	32,6 (19.1 - 80.8)	11.7 (4.9 - 29.6)	< 0.0001
Ferritin, µg/L	363.0 (7.0 - 50.55)	468.5 (271.0 - 894.5)	268.0 (148.0 - 492.0)	0.0004
D-dimer, mg/L	0.4 (0.29 - 0.62)	0.46 (0.29 - 0.74)	0.36 (0.29 - 0.56)	0.148
CT-grade pulmonary injury, %	25 (15 - 35)	30 (25 - 45)	20 (15 - 30)	0.0001
Concomitant diseases, n (%)
Hypertension	69 (69)	30 (68.2)	39 (69.6)	0.760
Dyslipidemia	49 (49)	24 (54.6)	25 (44.6)	0.158
Obesity	43 (43)	21 (47.7)	22 (39.3)	0.200
Diabetes	4 (4)	2 (4.5)	2 (3.6)	0.734
CHD	12 (12)	6 (13.6)	6 (10.7)	0.522
CKD (GFR < 60 mL/min/1.73 m²)	16 (16)	9 (20.5)	7 (12.6)	0.133
CHF	11 (11)	4 (9.1)	7 (12.5)	0.367

Table 1. Main Clinical and Demographic Characteristics of Patients With COVID-19

Total group (n = 100)

Severe course (n = 44)

Moderate course (n = 56)

Р value

P values for the group of severe vs. moderate COVID-19. CHD: coronary heart disease; CHF: chronic heart failure; CKD: chronic kidney disease; CRP: C-reactive protein; CT: computed tomography; DBP: diastolic blood pressure; GFR: glomerular filtration rate; HR: heart rate; LDL-C: low-density lipoprotein-cholesterol; RR: respiratory rate; SBP: systolic blood pressure; SpO₂: average value of oxygen saturation measured with a pulse oximeter; TG: triglycerides.

Age, years

58.5 (50.5 - 69.0)

59.5 (49.5 - 70.0)

56.5 (51.5 - 68.0)

0.409

Male gender, n (%)

49 (49)

21 (47.7)

28 (50)

0.778

Smoking, n (%)

13 (13)

5 (11.4)

8 (14.3)

0.522

SBP, mm Hg

125 (120 - 134)

129.5 (120 - 134.5)

125 (120 - 132)

0.661

DBP, mm Hg

80 (74 - 84)

80 (74.5 - 85)

80 (75 - 84)

0.883

HR, beats/min

80 (75 - 88.5)

84 (78.5 - 90.0)

80.0 (74.0 - 88.0)

0.154

BMI, kg/m²

28.74 (24.84 - 32.49)

30.04 (26.22 - 32.87)

27.66 (24.64 - 31.62)

0.129

RR, /min

22 (21 - 23.5)

23 (22 - 24)

22 (21 - 22)

0.0004

SpO₂, %

94 (92 - 96)

92 (91 - 93)

96 (95 - 97)

< 0.0001

Glucose, mmol/L

6.11 (5.69 - 6.7)

6.22 (5.81 - 7.05)

6.07 (5.55 - 6.48)

0.105

TG, mmol/L

1.62 (1.15 - 2.22)

1.71 (1.21 - 2.53)

1.61 (1.11 - 2.09)

0.316

LDL-C, mmol/L

2.94 (2.37 - 3.84)

2.80 (2.19 - 3.87)

3.03 (2.57 - 3.70)

0.282

GFR, mL/min/1.73 m²

75.8 (64.5 - 84.6)

78.4 (62.95 - 86.1)

73.6 (65.0 - 82.5)

0.483

CRP, mg/L

19.8 (7.0 - 50.55)

32,6 (19.1 - 80.8)

11.7 (4.9 - 29.6)

< 0.0001

Ferritin, µg/L

363.0 (7.0 - 50.55)

468.5 (271.0 - 894.5)

268.0 (148.0 - 492.0)

0.0004

D-dimer, mg/L

0.4 (0.29 - 0.62)

0.46 (0.29 - 0.74)

0.36 (0.29 - 0.56)

0.148

CT-grade pulmonary injury, %

25 (15 - 35)

30 (25 - 45)

20 (15 - 30)

0.0001

Concomitant diseases, n (%)

Hypertension

69 (69)

30 (68.2)

39 (69.6)

0.760

Dyslipidemia

49 (49)

24 (54.6)

25 (44.6)

0.158

Obesity

43 (43)

21 (47.7)

22 (39.3)

0.200

Diabetes

4 (4)

2 (4.5)

2 (3.6)

0.734

CHD

12 (12)

6 (13.6)

6 (10.7)

0.522

CKD (GFR < 60 mL/min/1.73 m²)

16 (16)

9 (20.5)

7 (12.6)

0.133

CHF

11 (11)

4 (9.1)

7 (12.5)

0.367

**Table 2.** Frequency Distribution of Genotypes and Alleles of Studied Polymorphisms in Patients With Severe and Moderate COVID-19
			Severe (N = 44)	Moderate (N = 56)	χ² value and P value
ACE1: angiotensin-converting enzyme type 1; AGT: angiotensinogen; HWE: Hardy-Weinberg equilibrium.
AGT rs4762	Genotypes, %	C/C	72.8	78.6	2.246 0.325
		C/Т	22.7	19.6
		Т/Т	4.5	1.8
	Alleles, %	C	84.15	88.4	0.374 0.415
		Т	15.85	11.6
	HWE, P		0.277	0.544
ACE1 rs1799752	Genotypes, %	I/I	11.4	7.1	1.259 0.533
		I/D	15.9	14.3
		D/D	72.7	78.6
	Alleles, %	I	19.35	14.25	0.581 0.341
		D	80.65	85.75
	HWE, P		0.004	0.008
AGTR1 rs5186	Genotypes, %	A/A	52.3	69.6	9.341 0.009
		A/C	36.4	26.8
		C/C	11.4	3.6
	Alleles, %	A	70.4	83.0	4.705 0.031
		C	29.6	17.0
	HWE, P		0.468	0.642
AGTR2 rs1403543 males	Alleles, %	G	47.6	57.7	2.007 0.157
		A	52.4	42.3
	HWE, P		0.000	0.000
AGTR2 rs1403543 females	Genotypes, %	G/G	26.1	23.3	10.570 0.006
		G/A	56.5	40.0
		A/A	17.4	36.7
	Alleles, %	G	54.35	43.3	2.654 0.104
		A	45.65	56.7
	HWE, P		0.572	0.454

Table 2. Frequency Distribution of Genotypes and Alleles of Studied Polymorphisms in Patients With Severe and Moderate COVID-19

Severe (N = 44)

Moderate (N = 56)

χ² value and P value

ACE1: angiotensin-converting enzyme type 1; AGT: angiotensinogen; HWE: Hardy-Weinberg equilibrium.

AGT rs4762

Genotypes, %

C/C

72.8

78.6

2.246
0.325

C/Т

22.7

19.6

Т/Т

4.5

1.8

Alleles, %

84.15

88.4

0.374
0.415

15.85

11.6

HWE, P

0.277

0.544

ACE1 rs1799752

Genotypes, %

I/I

11.4

7.1

1.259
0.533

I/D

15.9

14.3

D/D

72.7

78.6

Alleles, %

19.35

14.25

0.581
0.341

80.65

85.75

HWE, P

0.004

0.008

AGTR1 rs5186

Genotypes, %

A/A

52.3

69.6

9.341
0.009

A/C

36.4

26.8

C/C

11.4

3.6

Alleles, %

70.4

83.0

4.705
0.031

29.6

17.0

HWE, P

0.468

0.642

AGTR2 rs1403543
males

Alleles, %

47.6

57.7

2.007
0.157

52.4

42.3

HWE, P

0.000

AGTR2 rs1403543
females

Genotypes, %

G/G

26.1

23.3

10.570
0.006

G/A

56.5

40.0

A/A

17.4

36.7

Alleles, %

54.35

43.3

2.654
0.104

45.65

56.7

HWE, P

0.572

0.454

**Table 3.** Haplotype Analysis Performed on ACE1 rs1799752, AGTR1 rs5186, and AGTR2 rs1403543 SNPs and Their Corresponding Frequencies in Moderate (N = 56) and Severe (N = 44) COVID-19
Haplotypes	Frequencies	P value
ACE1: angiotensin-converting enzyme type 1; AGT: angiotensinogen; SNPs: single nucleotide polymorphisms.
D	A	A	0.2712748	0.3190880	0.2054829	0.0750527
I	A	G	0.0347194	0.0417922	0.0255644	0.6474502
D	A	G	0.3910026	0.4057926	0.3753691	0.7787819
I	A	A	0.0780032	0.0636843	0.0981290	0.5735669
D	C	A	0.1034446	0.0977041	0.1155361	0.4660593
I	C	A	0.0472774	0.0284521	0.0694884	0.2323572
D	C	G	0.0692780	0.0345580	0.1104301	0.0495588
I	C	G	0.0050000	0.0089286	NA	NA

Table 3. Haplotype Analysis Performed on ACE1 rs1799752, AGTR1 rs5186, and AGTR2 rs1403543 SNPs and Their Corresponding Frequencies in Moderate (N = 56) and Severe (N = 44) COVID-19

Haplotypes

Frequencies

P value

rs1799752

rs5186

rs1403543

Total

Moderate

Severe

ACE1: angiotensin-converting enzyme type 1; AGT: angiotensinogen; SNPs: single nucleotide polymorphisms.

0.2712748

0.3190880

0.2054829

0.0750527

0.0347194

0.0417922

0.0255644

0.6474502

0.3910026

0.4057926

0.3753691

0.7787819

0.0780032

0.0636843

0.0981290

0.5735669

0.1034446

0.0977041

0.1155361

0.4660593

0.0472774

0.0284521

0.0694884

0.2323572

0.0692780

0.0345580

0.1104301

0.0495588

0.0050000

0.0089286