Polymorphism (-499C/G) in <i>DDAH2</i> promoter may act as a protective factor for metabolic syndrome: A case-control study in Azar-Cohort population

Faramarzi, Elnaz; Aftabi, Younes; Ansarin, Khalil; Somi, Mohammad Hossein; Gilani, Neda; Seyedrezazadeh, Ensiyeh

doi:10.20945/2359-3997000000391

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Original Article • Arch. Endocrinol. Metab. 65 (4) • 2021 • https://doi.org/10.20945/2359-3997000000391 copy

Polymorphism (-499C/G) in DDAH2 promoter may act as a protective factor for metabolic syndrome: A case-control study in Azar-Cohort population

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

Globally developing metabolic syndrome (MetS) prevalence as a major health problem can be related to multiple factors of genetic and environmental. Dimethylaminohydrolase 2 (DDAH2) is the main enzyme implicated in the cardiovascular system, which regulates the nitric oxide pathway. This study investigated the association of DDAH2 polymorphism −499C/G (rs805305) with the risk of MetS among the Azar-Cohort population.

Subjects and methods:

The occurrence of SNP rs805305 in the DDAH2 gene was tested using the PCR-RFLP method in 332 MetS cases and 294 healthy controls. Afterward, the association of the allele and genotypes with the risk of MetS and its components were examined.

Results:

The G allele and GC genotype were significantly associated with a reduced risk of MetS (P ≤ 0.001). Also, the dominant genetic model (GG+GC) significantly decreased the risk of MetS (P = 0.001), however, in sex subtypes MetS risk was significantly reduced in males before and in females after adjustment for age (P ≤ 0.02).

Conclusion:

The −499C/G polymorphism of DDAH2 may play a protective role and reduce MetS risk among the Azar-Cohort population.

Keywords
DDAH2 ; rs805305; polymorphism; metabolic syndrome; cohort study

Parameters	MetS Patients (n = 332)	Controls (n = 294)	Pvalue
Total	mean ± SD	mean ± SD	Pvalue
Age (years)	43.05 ± 4.44	41.70 ± 4.50	<0.001
Male n(%)	141 (42.5)	120 (40.8)
Female n(%)	191 (57.5)	174 (59.2)
Weight (kg)	85.11 ± 13.37	74.07 ± 13.16	<0.001
BMI (kg/m²)	32.01 ± 4.18	27.83 ± 4.93	<0.001
Waist circumference (cm)	99.33 ± 9.22	87.93 ± 10.19	<0.001
SBP (mmHg)	119.45 ± 14.49	111.95 ± 12.83	<0.001
DBP (mmHg)	79.22 ± 8.89	73.11 ± 8.59	<0.001
Glucose (mg/dL)	100.03 ± 14.97	91.35 ± 9.49	<0.001
Total cholesterol (mg/dL)	204.92 ± 43.53	187.48 ± 33.72	<0.001
LDL (mg/dL)	121.04 ± 34.45	114.59 ± 32.13	0.01
HDL (mg/dL)	40.27 ± 9.73	49.68 ± 11.59	<0.001
Triglycerides (mg/dL)	215.3 ± 120.88	120.23 ± 41.57	<0.001
Male	N = 141	N = 120
Age (years)	42.60 ± 4.40	42.29 ± 4.45	0.65
Weight (kg)	91.05 ± 13.79	77.21 ± 11.44	<0.001
BMI (kg/m²)	31.00 ± 3.84	25.96 ± 3.54	<0.001
Waist circumference (cm)	100.21 ± 9.22	88.10 ± 9.89	<0.001
SBP (mmHg)	121.98 ± 14.13	115.77 ± 14.09	<0.001
DBP (mmHg)	82.05 ± 9.88	75.57 ± 8.99	<0.001
Glucose (mg/dL)	103.02 ± 18.74	96.01 ± 8.96	<0.001
Total cholesterol (mg/dL)	205.54 ± 47.39	191.75 ± 37.58	0.01
LDL (mg/dL)	120.10 ± 42.86	119.16 ± 34.50	0.84
HDL (mg/dL)	36.09 ± 7.82	46.61 ± 10.86	<0.001
Triglycerides (mg/dL)	250.20 ± 153.94	129.83 ± 55.23	<0.001
Female	N = 191	N = 174
Age (years)	43.26 ± 4.46	41.43 ± 4.52	<0.001
Weight (kg)	80.75 ± 11.30	71.90 ± 13.85	<0.001
BMI (kg/m²)	32.72 ± 4.30	29.11 ± 5.34	<0.001
Waist circumference (cm)	97.99 ± 9.01	87.90 ± 10.56	<0.001
SBP (mmHg)	117.61 ± 14.50	109.31 ± 11.18	<0.001
DBP (mmHg)	77.17 ± 7.44	71.42 ± 7.90	<0.001
Glucose (mg/dL)	97.79 ± 11.04	88.14 ± 8.48	<0.001
Total cholesterol (mg/dL)	204.67 ± 40.56	185.97 ± 34.06	<0.001
LDL (mg/dL)	123.27 ± 33.69	111.44 ± 30.09	0.001
HDL (mg/dL)	43.06 ± 7.82	51.79 ± 11.64	<0.001
Triglycerides (mg/dL)	191.60 ± 82.05	113.62 ± 26.86	<0.001

Genotype/Allele	MetS Patients N (%)	Controls N (%)	Unadjusted Odds Ratio (95% CI)	Pvalue	^* * Adjusted odds ratio (95% CI) for age and sex in total sample of study; adjusted for age in both gender. *P < 0.05. Adjusted Odds Ratio (95% CI)	Pvalue
Total (N = 626)	(N = 332)	(N = 294)
CC	130 (39.2)	80 (27.4)		Reference
CG	133 (40.1)	158 (54.1)	0.51 (0.36-0.74)	<0.0001	0.50 (0.34-0.74)	0.001
GG	69 (20.8)	54 (18.5)	0.78 (0.5-1.23)	0.29	0.76 (0.45-1.29)	0.32
C	393 (59.2)	313 (53.6)		Reference
G	271 (40.8)	271 (46.4)	0.74 (0.63-0.99)	0.04	0.67 (0.54-0.86)	0.002
(GG+GC) vs. CC	202 (60.8) vs. 130 (39.2)	212 (72.6) vs. 80 (27.4)	0.58 (0.41-0.82)	0.002	0.56 (0.39-0.81)	0.002
HWE	X² = 9.69; P < 0.005	X² = 2.41; P > 0.05
Male (n = 259)	(N = 141)	(N = 118)
CC	45 (31.9)	23 (19.5)		Ref.
CG	61 (43.3)	68 (57.6)	0.45 (0.24-0.84)	0.01	0.49 (0.24-0.98)	0.04
GG	35 (24.8)	27 (22.9)	0.66 (0.32-1.34)	0.25	0.73 (0.28-1.87)	0.52
C	151 (53.5)	109 (46.4)		Ref.
G	131 (46.5)	127 (53.8)	0.74 (0.52-1.05)	0.09	0.89 (0.60-1.33)	0.58
(GG+GC) vs. CC	96 (68.1) vs. 45 (31.9)	95 (80.5) vs. 23 (19.5)	0.51 (0.29-0.92)	0.02	0.54 (0.28-1.04)	0.06
HWE	X2 = 2.4; P > 0.05	X2 = 2.79; P > 0.05
Female (n = 365)	(N = 191)	(N = 174)
CC	85 (44.5)	57 (32.8)		Ref.
CG	72 (37.7)	90 (51.7)	0.53 (0.34-0.84)	0.008	0.51 (0.32-0.82)	0.006
GG	34 (17.8)	27 (15.5)	0.84 (0.46-1.54)	0.58	0.78 (0.41-1.49)	0.46
C	242 (63.4)	204 (58.6)	Ref.
G	140 (36.6)	144 (41.4)	0.82 (0.6-1.10)	0.19	0.55 (0.40-0.77)	<0.0001
(GG+GC) vs. CC	106 (55.5) vs. 85 (44.5)	117 (67.2) vs. 57 (32.28)	0.60 (0.39-0.93)	0.22	0.57 (0.36-0.89)	0.01
HWE	X2 = 6.76; P < 0.01	X2 = 0.76; P > 0.05

	Total		Male		Female
	*Observed #	Expected #	*Observed #	Expected #	*Observed #	Expected #
CC	80	86.6	23	27.5	57	59.8
CG	158	144.8	68	58.9	90	84.4
GG	54	60.6	27	31.5	27	29.8
Chi-squared value	2.410		2.794		0.762
P value	0.121		0.095		0.383

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[1] Correspondence to: Ensiyeh Seyedrezazadeh, Tuberculosis and Lung Disease Research Center Pashmineh Research Complex, Daneshgah Street, Tabriz, Iran. E-mail: e.s.rezazadeh@tbzmed.ac.ir