Glomerular infiltration of monocytes/macrophages occurs in diabetic patients with nephropathy, and chemokine receptor signals are thought to play a key role in the development of nephropathy. Recently, polymorphism of the chemokine receptor (CCR)2 coding region V64I and the CCR5 promoter region 59029 (G/A) have been identified. Accordingly, we evaluated the effects of these genotypes on diabetic nephropathy. CCR2 V64I and CCR5 59029 (G/A) were detected by polymerase chain reaction–restriction fragment–length polymorphism in 401 patients with type 2 diabetes who had a serum creatinine <2.0 mg/dl. Although the CCR2 V64I genotype showed no association with nephropathy, the frequency of the CCR5 59029 A-positive genotype (G/A or A/A) was significantly higher in patients with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] ≥30 and <300 mg/gCre, 86%) and patients with macroalbuminuria (ACR ≥300 mg/gCre, 87%) than in patients with normoalbuminuria (ACR <30 mg/gCre, 75%; P = 0.0095). Polytomic logistic regression analysis showed that the CCR5 59029 A-positive genotype was associated with nephropathy (odds ratio 2.243, P = 0.0074). These results suggest that the CCR5 promoter 59029 A genotype may be an independent risk factor for diabetic nephropathy in patients with type 2 diabetes.

Monocyte/macrophage infiltration has been detected in the glomeruli of rats with streptozotocin-induced diabetes and in renal biopsy specimens from patients with diabetic nephropathy, suggesting that the secretion of chemokines is enhanced in diabetes and that monocyte recruitment to renal tissues and differentiation to macrophages may be associated with the development or progression of diabetic nephropathy (1,2,3,4). The overexpression of monocyte chemoattractant protein 1 (MCP-1) has been reported in human mesangial cells cultured under high-glucose conditions and in renal tissue from streptozotocin-induced diabetic rats (2,5). The diabetic state is thought to increase the production of cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β), probably through activation of protein kinase C, oxidative stress, and advanced glycosylation end product formation (6,7,8). In turn, TNF-α and IL-1β stimulate the expression of MCP-1 and another chemokine, which is known as regulated upon activation, normal T- cell expressed and secreted (RANTES), in human mesangial cells (9,10). Because the major receptor for MCP-1 and RANTES expressed on the surface of monocytes is chemokine receptor (CCR)2 and CCR5, respectively, CCR2- and CCR5-mediated monocyte recruitment and differentiation to macrophages in the glomerulus may play a key role in diabetic nephropathy (3,4).

Recently, a single nucleotide polymorphism (SNP), G/A at nucleotide position 46295, was identified in the open reading frame of CCR2 (11,12). The G-to-A substitution leads to replacement of valine by isoleucine at amino acid 64 (CCR2 V64I) in the first transmembrane domain of CCR2, and the 46295A genotype (CCR2 64I) has been reported to show an association with the progression of AIDS and with the development of sarcoidosis. Another SNP, G/A at nucleotide position 59029 in the promoter region of CCR5 (G59029A), has also been recently identified (13). Although the motif linked with the 59029 site has not been elucidated, an increase of CCR5 expression by peripheral blood mononuclear cells has been observed in individuals with the CCR5 59029A genotype (14); therefore, this genotype is thought to be associated with CCR5 gene expression. Interestingly, both the CCR2 and CCR5 genes are located on chromosome 3p21 at a distance of between 65.1 and 67.7 cM, a site that was reported to possibly show an association with diabetic nephropathy by sib-pair linkage analysis in Pima Indians (15). Because the significance of these genotypes has not been analyzed in diabetes, we evaluated the association of CCR2 and CCR5 polymorphisms with diabetic nephropathy in Japanese patients with type 2 diabetes. We simultaneously determined an ACE intron 16 insertion/deletion polymorphism, which is a possible genetic factor associated with nephropathy (16,17).

The clinical characteristics of the subjects are shown in Table 1. Although the estimated duration of diabetes was significantly longer in the microalbuminuria group (DN1 group, urinary albumin-to-creatinine ratio [ACR] ≥30 and <300 mg/g Cre) and in the macroalbuminuria group (DN2 group, ACR ≥300 mg/g Cre) than in the normoalbuminuria group (DN0 group, ACR <30 mg/g Cre), there was no significant difference between the other two groups. The percentage of patients with hypertension showed a significant increase along with the severity of nephropathy, but frequencies of the hypertension patients using an ACE inhibitor were not different among the three groups. HbA1c was significantly higher in the DN2 group than in the DN0 or DN1 groups. Total cholesterol was significantly higher in the DN2 group than in the DN0 group. The plasma triglyceride and HDL cholesterol levels of the DN1 and DN2 groups were significantly higher and lower than those of the DN0 group, respectively, whereas no significant differences were observed between the DN1 and DN2 groups. The percentage of cardiovascular disease (CVD; stroke or ischemic heart disease) was significantly higher in the DN1 and the DN2 groups than in the DN0 group, but frequencies of the current smokers were not different among the three groups. ACE genotypes did not differ among the three groups.

The distribution of CCR2 and CCR5 genotypes is shown in Table 2. The frequency of the CCR2 64I and CCR5 59029A alleles was 28 and 54%, respectively, which was consistent with the Hardy-Weinberg equilibrium. Two SNPs were in linkage disequilibrium. CCR2 64I homozygosity was not found in subjects with the CCR5 59029G allele, while CCR5 59029G homozygosity was not observed in subjects with the CCR2 64I allele. Thus, we could only observe six combinations of the two genotypes.

The characteristics of subjects classified by their CCR2 and CCR5 genotypes are shown in Table 3. Clinical parameters and ACE genotypes did not differ among the groups classified on the basis of CCR2 and CCR5 genotypes.

The frequencies of the genotypes in groups classified by the stage of nephropathy are shown in Table 4. The DN0 group showed a significantly higher frequency of the CCR5 G/G genotype and a lower frequency of the G/A and A/A genotypes than the DN1 or DN2 groups (P = 0.033, χ2 = 6.824: DN0 group vs. DN1 and DN2 groups). Thus, the DN0 group had fewer patients with an A-positive genotype (G/A or A/A) than the DN1 and DN2 groups (P = 0.029, χ2 = 4.794: DN0 group vs. DN1 group; P = 0.0095, χ2 = 6.734: DN0 group vs. DN1 and DN2 groups; P = 0.096, χ2 = 2.778: DN0 group vs. DN2 group). In contrast, there was no difference in the frequency of CCR5 genotypes between the DN1 and DN2 groups. The DN0 group showed a higher frequency of the CCR2 genotype Wt(64V) and a lower frequency of the Wt/64I and 64I/64I genotypes than the DN1 or DN2 groups, but there were no significant differences. ACE insertion/deletion polymorphism showed no differences among the three groups.

Polytomic logistic regression analysis using stepwise forward selection was done to assess the relationship between nephropathy and the clinical factors listed in Table 1 or the CCR2 and CCR5 genotypes. As shown in Table 5, the estimated duration of diabetes, hypertension, HbA1c, plasma triglycerides, and a CCR5 A-positive genotype (G/A or A/A), but not the CCR2 64I or ACE D-positive genotypes, were significantly associated with nephropathy.

In the present study, we evaluated whether the CCR2 coding region 46295 genotype (V64I) or the CCR5 promoter region 59029 G/A genotype was associated with diabetic nephropathy. To avoid the confounding influence of the ACE I/D genotype, a possible genetic factor associated with nephropathy, this genotype was assessed simultaneously, and we confirmed that there were no differences in its distribution among subjects, classified by the stage of nephropathy or by their CCR2 and CCR5 genotypes. The overall allele frequency of CCR2 64I and CCR5 59029A in our subjects with type 2 diabetes was 28 and 54%, respectively. Although the CCR2 64I allele frequency was similar to that previously reported in healthy Japanese subjects (CCR2 64I: 26.2%) (12), the CCR5 59029A frequency has not yet been examined in a healthy Japanese population. Although the CCR2 V64I genotype was not associated with nephropathy, a CCR5 59029 A-positive genotype was significantly more common in the groups with microalbuminuria or macroalbuminuria than in the group with normoalbuminuria. Furthermore, polytomic logistic regression analysis showed that the CCR5 59029 A-positive genotype was significantly correlated to nephropathy. Therefore, the CCR5 59029 A-positive genotype may be an independent risk factor for nephropathy.

A previous immunohistological study of renal biopsy tissues from type 2 diabetic subjects with nephropathy has shown that the number of infiltrating monocytes and macrophages in the glomeruli is increased in the mild stage of glomerulosclerosis when compared with nondiabetic control subjects and that a marked further increase occurs in the moderate stage of glomerulosclerosis (1). These results suggest that monocyte infiltration and differentiation into macrophages may contribute to the development of nephropathy and to irreversible glomerular damage, so that CCR5-mediated signals may play a significant role in progression of nephropathy from microalbuminuria to macroalbuminuria and end-stage renal failure. Therefore, a large-scale cross-sectional prospective study of the association between the CCR5 59029 genotype and progression of nephropathy should be performed in the future.

Chemokine signals are thought to be important in the development of atherosclerosis as well as nephropathy. CCR2 and CCR5 expression by smooth muscle cells and monocytes in the vascular wall is reported to be stimulated by several cytokines or lipoproteins, suggesting that CCR-mediated signals may play a key role in the development of atherosclerosis (4,18,19,20). We also evaluated the carotid artery intima-media thickness (IMT) by B-mode ultrasonography in some of our subjects and found that CCR5 59029 A-positive or CCR2 64I-positive patients had a greater mean IMT than those without these genotypes (data not shown). Furthermore, the DN1 and DN2 groups showed a higher percentage of CVD than the DN0 group; therefore, we cannot deny a possibility of bias from CVD. Further study may help to clarify whether these genotypes are independently associated with macroangiopathy.

In conclusion, we found an association of the CCR5 promoter genotype with the early stage of nephropathy in Japanese patients with type 2 diabetes. It is necessary to confirm the effect of this genotype on nephropathy by a large-scale cross-sectional prospective study, the results of which may contribute to clarifying the mechanism behind the development or progression of diabetic nephropathy.

A total 401 Japanese patients with type 2 diabetes (266 men and 135 women aged 60.8 ± 0.4 years; mean ± SE) were recruited from the outpatient clinic of Juntendo University Hospital (Tokyo). Because chronic renal failure tends to complicate severe atherosclerosis, we excluded patients showing a serum creatinine level ≥2.0 mg/dl to minimize the bias of atherosclerosis. Patients having other evidence of renal disease were also excluded. All subjects gave written informed consent before enrollment in the study, which was approved by the Ethics Committee of Juntendo University. Hypertension was defined as a systolic blood pressure >140 mmHg and/or a diastolic blood pressure >90 mmHg or the use of oral antihypertensive therapy. The stage of nephropathy was determined from the average of at least two measurements of ACR, and the subjects were classified into the following three groups: a normoalbuminuria group (DN0 group, ACR <30 mg/gCre), a microalbuminuria group (DN1 group, ACR ≥30 and <300 mg/gCre), and a macroalbuminuria group (DN2 group, ACR ≥300 mg/gCre).

Genomic DNA was extracted from peripheral blood cells using a DNA extraction kit (QIAamp DNA Blood Kit; Qiagen, Tokyo). CCR2 V64I was determined by polymerase chain reaction (PCR)-restriction fragment–length polymorphism (RFLP) analysis, as previously described (12). Briefly, genomic DNA was amplified by the PCR using a forward primer (5′-TTG TGG GCA ACA TGa TGG-3′: CCR2-F) and a reverse primer (5′-CTG TGA ATA ATT TGC ACA TTG C-3′: CCR2-R). CCR2-F had a substitution from cytosine to adenine (shown by the lower-case “a”) for creation of the digest site. PCR products were digested with Bsa BI (New England Biolabs, Beverly, MA) for 3 h at 60°C and then electrophoresed on 4% NuSieve (3:1) gel (FMC BioProducts, Roland, ME) and stained with ethidium bromide. CCR5 G59029A was also detected by PCR-RFLP, as described elsewhere (13). Briefly, genomic DNA was amplified using a forward primer (5′-CCC GTG AGC CCA TAG TTA AAA CTC-3′) and a reverse primer (5′-TCA CAG GGC TTT TCA ACA GTA AGG-3′). The PCR products were digested with Bsp 1 286I (New England Biolabs) for 5 h at 37°C. The restriction site was found in the G allele of 59029 but not in the A allele. After digestion, the products were electrophoresed on 2% agarose gel and stained with ethidium bromide. Insertion or deletion at intron 16 of the ACE gene was detected by PCR, as previously described (16). Briefly, genomic DNA was amplified by using a forward primer (5′-CTG GAG ACC ACT CCC ATC CTT TCT-3′) and a reverse primer (5′-GAT GTG GCC ATC ACA TTC GTC AGA T-3′), after which the PCR products were electrophoresed on 2% agarose gel and stained with ethidium bromide. Insertion and deletion of the allele was detected as a band of 490 and 190 bp, respectively.

Data are expressed as the means ± SE. The statistical significance of differences in mean values was analyzed by one-way analysis of variance, followed by Scheffe’s multiple comparison test, and the significance of differences in frequency was determined by the χ2 test. To assess the relationship of the CCR2 and CCR5 genotypes with nephropathy, polytomic logistic regression analysis was performed using the SAS statistical package (SAS Institute, Cary, NC).

TABLE 1

Clinical characteristics

All subjectsStage of nephropathy
Normoalbuminuria (DN0)Microalbuminuria (DN1)Macroalbuminuria (DN2)
n 401 269 93 39 
M/F (% male) 266/135 (66) 171/98 (64) 66/27 (71) 29/10 (74) 
Age (years) 60.8 ± 0.4 60.0 ± 0.5 61.7 ± 1.0 63.9 ± 1.6* 
Duration (years) 11.7 ± 0.4 10.3 ± 0.5 14.2 ± 1.0* 15.4 ± 1.6* 
BMI (kg/m2) 22.9 ± 0.2 22.7 ± 0.2 23.3 ± 0.4 23.4 ± 0.5 
Hypertension/nonhypertension (% hypertension) 164/237 (41) 91/178 (34) 46/47 (49)* 27/12 (69)*‡ 
ACE inhibitor (% ACEi/hypertension) 42 (26) 22 (24) 12 (26) 8 (30) 
HbA1c (%) 7.31 ± 0.1 7.18 ± 0.09 7.39 ± 0.15 7.99 ± 0.26*‡ 
Total cholesterol (mg/dl) 196.2 ± 2.0 192.8 ± 2.2 198.1 ± 4.4 215.2 ± 9.4* 
HDL cholesterol (mg/dl) 55.0 ± 0.8 56.5 ± 1.0 52.4 ± 1.6† 50.5 ± 2.2† 
Triglycerides (mg/dl) 171.8 ± 10.7 149.6 ± 7.5 203.2 ± 25.7* 249.8 ± 75.2* 
CVD 64 (16) 33 (12) 22 (24)† 9 (23)† 
Smoker 114 (28) 81 (30) 22 (24) 11 (28) 
Serum creatinine (mg/dl) 0.76 ± 0.01 0.70 ± 0.01 0.79 ± 0.02* 1.05 ± 0.06*§ 
ACR 215.8 ± 42.6 11.0 ± 0.5 104.2 ± 8.1* 1855.5 ± 305.2*§ 
ACE insertion/deletion (II/ID/DD) 167/183/51 114/118/37 33/48/12 20/17/2 
All subjectsStage of nephropathy
Normoalbuminuria (DN0)Microalbuminuria (DN1)Macroalbuminuria (DN2)
n 401 269 93 39 
M/F (% male) 266/135 (66) 171/98 (64) 66/27 (71) 29/10 (74) 
Age (years) 60.8 ± 0.4 60.0 ± 0.5 61.7 ± 1.0 63.9 ± 1.6* 
Duration (years) 11.7 ± 0.4 10.3 ± 0.5 14.2 ± 1.0* 15.4 ± 1.6* 
BMI (kg/m2) 22.9 ± 0.2 22.7 ± 0.2 23.3 ± 0.4 23.4 ± 0.5 
Hypertension/nonhypertension (% hypertension) 164/237 (41) 91/178 (34) 46/47 (49)* 27/12 (69)*‡ 
ACE inhibitor (% ACEi/hypertension) 42 (26) 22 (24) 12 (26) 8 (30) 
HbA1c (%) 7.31 ± 0.1 7.18 ± 0.09 7.39 ± 0.15 7.99 ± 0.26*‡ 
Total cholesterol (mg/dl) 196.2 ± 2.0 192.8 ± 2.2 198.1 ± 4.4 215.2 ± 9.4* 
HDL cholesterol (mg/dl) 55.0 ± 0.8 56.5 ± 1.0 52.4 ± 1.6† 50.5 ± 2.2† 
Triglycerides (mg/dl) 171.8 ± 10.7 149.6 ± 7.5 203.2 ± 25.7* 249.8 ± 75.2* 
CVD 64 (16) 33 (12) 22 (24)† 9 (23)† 
Smoker 114 (28) 81 (30) 22 (24) 11 (28) 
Serum creatinine (mg/dl) 0.76 ± 0.01 0.70 ± 0.01 0.79 ± 0.02* 1.05 ± 0.06*§ 
ACR 215.8 ± 42.6 11.0 ± 0.5 104.2 ± 8.1* 1855.5 ± 305.2*§ 
ACE insertion/deletion (II/ID/DD) 167/183/51 114/118/37 33/48/12 20/17/2 

Data are the means ± SE or n (%).

*

P < 0.01 (vs. DN0);

†

P < 0.05 (vs. DN0);

‡

P < 0.05 (vs. DN1)

§

P < 0.01 (vs. DN1).

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TABLE 2

CCR5 promoter and CCR2 64I genotype combinations

CCR2 64ICCR5 promoter genotype
G/GG/AA/A
Wt/Wt 85 96 26 
Wt/64I 0 103 58 
64I/64I 0 0 33 
CCR2 64ICCR5 promoter genotype
G/GG/AA/A
Wt/Wt 85 96 26 
Wt/64I 0 103 58 
64I/64I 0 0 33 
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TABLE 3

Clinical characteristics of the CCR5 and CCR2 genotypes

CCR5
CCR2
G/GG/AA/AWt/WtWt/64I64I/64I
n 85 199 117 207 161 33 
M/F (% male) 55/30 (65) 131/68 (66) 80/37 (68) 139/68 (67) 103/58 (64) 24/9 (73) 
Age (years) 59.8 ± 1.0 61.4 ± 0.6 60.5 ± 0.7 60.5 ± 0.6 61.3 ± 0.7 60.2 ± 1.6 
Duration (years) 10.9 ± 0.9 12.2 ± 0.6 11.4 ± 0.8 11.2 ± 0.6 12.5 ± 0.7 10.8 ± 1.6 
BMI (kg/m2) 23.2 ± 0.4 22.6 ± 0.2 23.2 ± 0.3 22.9 ± 0.2 22.7 ± 0.3 23.9 ± 0.7 
Hypertension/nonhypertension (% hypertension) 35/50 (41) 78/121 (39) 51/66 (44) 76/131 (37) 71/90 (44) 17/16 (52) 
HbA1c (%) 7.41 ± 0.16 7.18 ± 0.10 7.45 ± 0.14 7.26 ± 0.10 7.40 ± 0.12 7.17 ± 0.22 
Total cholesterol (mg/dl) 197.2 ± 5.4 193.7 ± 2.7 199.6 ± 3.4 193.8 ± 3.1 199.1 ± 2.9 196.6 ± 4.7 
HDL cholesterol (mg/dl) 53.7 ± 1.9 55.6 ± 1.1 54.9 ± 1.6 53.8 ± 1.1 57.6 ± 1.4 49.6 ± 2.2 
Triglycerides (mg/dl) 191.1 ± 35.5 155.5 ± 8.6 185.4 ± 21.9 182.1 ± 19.4 153.9 ± 8.7 194.1 ± 19.4 
ACE insertion/deletion (II/ID/DD) 37/38/10 82/89/28 48/56/13 85/94/28 73/71/17 9/18/6 
CCR5
CCR2
G/GG/AA/AWt/WtWt/64I64I/64I
n 85 199 117 207 161 33 
M/F (% male) 55/30 (65) 131/68 (66) 80/37 (68) 139/68 (67) 103/58 (64) 24/9 (73) 
Age (years) 59.8 ± 1.0 61.4 ± 0.6 60.5 ± 0.7 60.5 ± 0.6 61.3 ± 0.7 60.2 ± 1.6 
Duration (years) 10.9 ± 0.9 12.2 ± 0.6 11.4 ± 0.8 11.2 ± 0.6 12.5 ± 0.7 10.8 ± 1.6 
BMI (kg/m2) 23.2 ± 0.4 22.6 ± 0.2 23.2 ± 0.3 22.9 ± 0.2 22.7 ± 0.3 23.9 ± 0.7 
Hypertension/nonhypertension (% hypertension) 35/50 (41) 78/121 (39) 51/66 (44) 76/131 (37) 71/90 (44) 17/16 (52) 
HbA1c (%) 7.41 ± 0.16 7.18 ± 0.10 7.45 ± 0.14 7.26 ± 0.10 7.40 ± 0.12 7.17 ± 0.22 
Total cholesterol (mg/dl) 197.2 ± 5.4 193.7 ± 2.7 199.6 ± 3.4 193.8 ± 3.1 199.1 ± 2.9 196.6 ± 4.7 
HDL cholesterol (mg/dl) 53.7 ± 1.9 55.6 ± 1.1 54.9 ± 1.6 53.8 ± 1.1 57.6 ± 1.4 49.6 ± 2.2 
Triglycerides (mg/dl) 191.1 ± 35.5 155.5 ± 8.6 185.4 ± 21.9 182.1 ± 19.4 153.9 ± 8.7 194.1 ± 19.4 
ACE insertion/deletion (II/ID/DD) 37/38/10 82/89/28 48/56/13 85/94/28 73/71/17 9/18/6 

Data are the means ± SE or n (%).

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TABLE 4

Distribution of CCR5 promoter, CCR 2 64I, and ACE I/D genotypes

All subjectsStage of nephropathy
Normoalbuminuria (DN0)Microalbuminuria (DN1)Macroalbuminuria (DN2)
n 401 269 (100) 93 (100) 39 (100) 
Genotype     
CCR5 promoter G/A     
 G/G 85 67 (25) 13 (14) 5 (13) 
 G/A 199 126 (47) 52 (56) 21 (54) 
 A/A 117 76 (28) 28 (30) 13 (33) 
 P = 0.033 for DN0 vs. DN1 and DN2 
CCR5 promoter G/A     
 G/G 85 67 (25) 13 (14) 5 (13) 
 G/A and A/A 316 202 (75) 80 (86) 34 (87) 
 P = 0.029 for DN0 vs. DN1 
 P = 0.0095 (DN0 vs 1 and 2)     
 CCR5 promoter A allele frequency 54% 52% 58% 60% 
CCR2 64I     
 Wt/Wt 207 146 (54) 41 (44) 20 (51) 
 Wt/64I 161 105 (39) 42 (45) 14 (36) 
 64I/64I 33 18 (7) 10 (11) 5 (13) 
 CCR2 64I allele frequency 28% 26% 33% 31% 
ACE insertion/deletion     
 I/I 167 114 33 20 
 I/D 183 118 48 17 
 D/D 51 37 12 2 
 ACE deletion allele frequency 36% 36% 39% 27% 
All subjectsStage of nephropathy
Normoalbuminuria (DN0)Microalbuminuria (DN1)Macroalbuminuria (DN2)
n 401 269 (100) 93 (100) 39 (100) 
Genotype     
CCR5 promoter G/A     
 G/G 85 67 (25) 13 (14) 5 (13) 
 G/A 199 126 (47) 52 (56) 21 (54) 
 A/A 117 76 (28) 28 (30) 13 (33) 
 P = 0.033 for DN0 vs. DN1 and DN2 
CCR5 promoter G/A     
 G/G 85 67 (25) 13 (14) 5 (13) 
 G/A and A/A 316 202 (75) 80 (86) 34 (87) 
 P = 0.029 for DN0 vs. DN1 
 P = 0.0095 (DN0 vs 1 and 2)     
 CCR5 promoter A allele frequency 54% 52% 58% 60% 
CCR2 64I     
 Wt/Wt 207 146 (54) 41 (44) 20 (51) 
 Wt/64I 161 105 (39) 42 (45) 14 (36) 
 64I/64I 33 18 (7) 10 (11) 5 (13) 
 CCR2 64I allele frequency 28% 26% 33% 31% 
ACE insertion/deletion     
 I/I 167 114 33 20 
 I/D 183 118 48 17 
 D/D 51 37 12 2 
 ACE deletion allele frequency 36% 36% 39% 27% 

Data are n or n (%), unless otherwise noted.

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TABLE 5

Polytomic logistic regression analysis of factors related to diabetic nephropathy

Odds ratio95% CIP
Duration of diabetes 1.049 1.024–1.075 <0.0001 
Hypertension 2.407 1.559–3.718 <0.0001 
HbA1c 1.178 1.018–1.363 0.0278 
Triglycerides 1.001 1.000–1.002 0.0043 
CCR5 A-positive genotype 2.243 1.241–4.051 0.0074 
Odds ratio95% CIP
Duration of diabetes 1.049 1.024–1.075 <0.0001 
Hypertension 2.407 1.559–3.718 <0.0001 
HbA1c 1.178 1.018–1.363 0.0278 
Triglycerides 1.001 1.000–1.002 0.0043 
CCR5 A-positive genotype 2.243 1.241–4.051 0.0074 
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Address correspondence and reprint requests to Yasushi Tanaka, MD, Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: [email protected].

Received for publication 9 May 2001 and accepted in revised form 12 October 2001.

ACR, albumin-to-creatinine ratio; CCR, chemokine receptor; CVD, cardiovascular disease; IL-1β, interleukin-1β; IMT, intima-media thickness; MCP-1, monocyte chemoattractant protein 1; PCR, polymerase chain reaction; RANTES, regulated upon activation, normal T-cell expressed and secreted; RFLP, restriction fragment–length polymorphism; SNP, single-nucleotide polymorphism; TNF-α, tumor necrosis factor-α.

2002