Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

Table 1 Demographic and clinical characteristics of patients

Parameter	Type 2 diabetes mellitus with nephropathy
Number of patients (n)	270
Gender (male/female)	128/142
Age (yr)	52.23 ± 6.011
Duration of diabetes (yr)	8.31 ± 3.091
Family history of diabetes (yes/no)	105/165
Family history of hypertension (yes/no)	63/207
Medications
Insulin (yes/no)	115/155
Metformin (yes/no)	153/117
Glimiperide (yes/no)	129/141

¹Data are presented as mean ± SD.

Table 2 Biochemical parameters before and after treatment with angiotensin converting enzyme inhibitor

Parameter	Baseline1	6 mo1,2	P-value
No. of patients	n = 252	n = 252
Blood urea (mmol/L)	2.22 ± 0.86	2.01 ± 0.77	0.661
Serum creatinine (μmol/L)	95.47-30	99-28.28	0.068
Serum sodium (mmol/L)	139.47 ± 4.11	135.14 ± 3.88	0.512
Serum potassium (mmol/L)	4.32 ± 0.65	4.30 ± 0.52	0.141
eGFR (MDRD) mL/min per 1.73 m2	73.65 ± 24.71	68.90 ± 24.44	0.081
eGFR (EPI) mL/min per 1.73 m2	73.40 ± 22.8	70.56 ± 21.30	0.07
Fasting plasma glucose (mmol/L)	7.63 ± 0.60	6.693 ± 0.81	0.08
Post-prandial plasma glucose (mmol/L)	10.33 ± 1.62	8.52 ± 1.3	0.076
HbA1c (%)	6.52 ± 1.71	6.1 ± 1.14	0.06
Hemoglobin (g/L)	123.8 ± 23	111.2 ± 31	0.65
Systolic blood pressure (mmHg)	132.30 ± 13.67	130.12 ± 10.46	0.71
Diastolic blood pressure (mmHg)	86.10 ± 10.03	84.07 ± 8.32	0.68

¹Data are presented as mean ± SD;

²P > 0.05. HbA1c: Hemoglobin A1c; eGFR: Estimated glomerular filtration rate.

Table 3 Responders and non-responders before and after treatment with angiotensin converting enzyme inhibitor therapy

Patients	Urinary ACR at baseline1	Urinary ACR at 6 mo	P-value	R2 (%)	NR (%)
Overall (n = 252)	185.97 (55.66-222.20)	118.64 (96.24-146.26)	< 0.001	121	131
Micro-albumin (n = 170)	78.79 (71.30-87.07)	53.67 (44.46-64.79)	< 0.001	76	94
Macro-albumin (n = 82)	1068.7 (879.62–1298.28)	596.45 (451.60-787.68)	< 0.001	45	37

¹Median (IQR);

²A decline of > 30% in ACR value at 6 mo is considered as R. R: Responders; NR: Non-responders; ACR: Albumin/creatinine ratio.

Table 4 Genotype distributions and allele frequency for angiotensin converting enzyme and angiotensinogen gene polymorphisms

Gene	n = 252	Genotype/allele	Percentage (%)
ACE (I/D)	Genotypic frequency	II	31
		ID	53
		DD	16
	Allele frequency	I	57
		D	43
AGT (M235T)	Genotypic frequency	MM	25
		MT	53
		TT	22
	Allele frequency	M	51
		T	49

ACE: Angiotensin converting enzyme; AGT: Angiotensinogen.

Table 5 Genotypic distribution of responders and non-responders

Gene	Genotype	No. of patients (n = 252)	At 6 mo follow-up		P-value1
			R (%) (n = 121)	NR (%) (n = 131)
ACE (I/D)	II	78	38 (49)	40 (51)	0.893
	ID	133	62 (47)	71 (53)
	DD	41	21 (51)	20 (49)
AGT (M235T)	MM	61	34 (56)	27 (44)	0.369
	MT	134	59 (44)	75 (56)
	TT	57	28 (49)	29 (51)

¹P > 0.05: Comparison between R or NR. ACE: Angiotensin converting enzyme; AGT: Angiotensinogen; R: Responders; NR: Non-responders.

Table 6 Genotypic distribution of responders and non-responders having micro-/ macro-albuminuria

Gene	Genotype (n = 252)	Micro-albuminuric group (n = 170)			Macro-albuminuric group (n = 82)
		R (%) (n = 76)	NR (%) (n = 94)	P-value1	Rc (%) (n = 45)	NR (%) (n = 37)	P-value2
ACE (I/D)	II	23 (45)	28 (55)	0.974	15 (56)	12 (44)	0.636
	ID	42 (44)	53 (56)		20 (53)	18 (47)
	DD	11 (49)	13 (54)		10 (59)	7 (41)
AGT (M235T)	MM	25 (60)	17 (40)	0.11	9 (47)	10 (53)	0.201
	MT	36 (40)	53 (60)		23 (51)	22 (49)
	TT	15 (38)	24 (62)		13 (72)	5 (28)

¹P > 0.05: Comparison between responders and non-responders to therapy in micro-albuminuric group;

²P > 0.05: Comparison between responders and non-responders to therapy in macro-albuminuric group. ACE: Angiotensin converting enzyme; AGT: Angiotensinogen; R: Responders; NR: Non-responders.