Apolipoprotein E2, renal failure and lipid abnormalities in non-insulin-dependent diabetes mellitus

Horita, Kazutoshi; Eto, Masashi; Makino, Isao

doi:10.1016/0021-9150(94)90021-3

Cited by 48 publications

(32 citation statements)

References 36 publications

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“…Our findings regarding the APOE polymorphism as the genetic risk factor for DN are consistent with the results of previous case-control studies in Japanese subjects with type 2 diabetes (7,8). Eto et al (8) reported that the carriers of the ⑀2 allele had an odds ratio of 3.0 (95% CI 1.2-7.7) for DN (135 control and 146 case subjects).…”

Section: Discussionsupporting

confidence: 91%

“…Recently, this ⑀2/⑀3/⑀4 polymorphism of APOE has been investigated for the association with DN in subjects with both type 1 and type 2 diabetes using a case-control comparison, but the findings were inconclusive (7)(8)(9)(10)(11)(12)(13)(14)(15). Very recently, we reported that the ⑀2 allele of APOE increases the risk of DN in type 1 diabetes in a large number of case-control comparisons and a family-based study called the transmission/disequilibrium test (16).…”

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confidence: 99%

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APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes

et al. 2003

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OBJECTIVE -The aim of this study is to clarify the conflicting results of the ⑀2/⑀3/⑀4 APOE polymorphism as a risk factor on diabetic nephropathy by a cohort study. RESEARCH DESIGN AND METHODS-A total of 429 Japanese subjects with type 2 diabetes and with normoalbuminuria (n ϭ 299) or with microalbuminuria (n ϭ 130) were enrolled in a prospective observational follow-up study during 1995-1998 and followed until 2001 (for at least 3 years). The endpoint was the occurrence of a renal event defined as the progression to a higher stage of diabetic nephropathy.RESULTS -During the study (the mean follow-up period: 4.4 Ϯ 1.0 years), 31 of 429 subjects progressed: 21 from normoalbuminuria to microalbuminuria and 10 from microalbuminuria to overt proteinuria. The allele frequency of the APOE polymorphism was significantly different between the progressors and the nonprogressors. Eight of 42 ⑀2 carriers (19%) progressed, whereas 23 of 387 noncarriers (6%) progressed with a relative risk of 3.2 (95% CI 1.5-6.7). When subjects were stratified by renal status at baseline, each relative risk for the progression in the ⑀2 carriers was 2.7 (0.99 -7.4) in those with normoalbuminuria and 4.2 (1.3-13.3) in those with microalbuminuria. Furthermore, when analyzed only in subjects with normoalbuminuria and short duration of diabetes (Ͻ15 years) at baseline, the risk in the ⑀2 carriers became higher to 3.2 (1.2-8.8).CONCLUSIONS -Our follow-up study indicates that the ⑀2 allele of the APOE polymorphism is a prognostic risk factor for both the onset and the progression of diabetic nephropathy in Japanese type 2 diabetes. Diabetes Care 26:2416 -2420, 2003D iabetic nephropathy (DN) associated with type 2 diabetes is a leading cause of end-stage renal disease (ESRD) in Japan and the U.S. (1,2). Although long-standing hyperglycemia is an important risk factor for the development of DN, epidemiologic and family studies suggest that genetic susceptibility to this complication is also required (3). The abnormalities of lipid metabolism have been proposed as one plausible mechanism in the pathogenesis of the development of DN (4). Thus, the genes encoding components of this pathway that regulate lipid metabolism can be considered as candidate genes susceptible to DN (5).Apolipoprotein E (apoE) is a 299-amino acid glycoprotein that plays a central role in lipid metabolism. ApoE is well known to consist of three common isoforms (E2, E3, E4) encoded by three alleles (⑀2, ⑀3, ⑀4) in exon 4 of the apoE gene (APOE) (6). The lipid profiles or atherogenic factors are, in part, determined by this genetic variation of APOE (6). Carriers of apoE4 have higher plasma levels of total cholesterol and low-density lipoprotein cholesterol than carriers of apoE2 or apoE3 homozygotes (6). On the other hand, the binding of apoE2 to lipoprotein receptors is defective in comparison with that of E3 or E4 and results in delayed clearance of triglyceride (TG)-rich lipoprotein.Recently, this ⑀2/⑀3/⑀4 polymorphism of APOE has been investigated for the association with DN ...

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes

et al. 2003

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“…Two previous studies (n = 162 and 252) did, however, find an association [17,19]. Two out of three studies in patients with Type II (non-insulin-dependent) diabetes mellitus found that the e2 allele was associated with increased risk of nephropathy [31,39,40]. One reason for these conflicting results is that previous studies had smaller numbers of diabetic patients with an e2 allele than our study [17,18,19,31,39,40].…”

Section: Discussioncontrasting

confidence: 88%

“…The other three studies of e2 allele and nephropathy in Type I diabetes did not examine the relation between the e2 allele and triglyceride concentration [17,18,19]. Most previous studies in Type II diabetes, that found that the e2 allele is associated with the development of diabetic nephropathy also found an increased concentration of triglyceride in patients with any e2 allele compared with those without [31,39] but they did not adjust for triglyceride.…”

Section: Discussionmentioning

confidence: 98%

Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients

et al. 2000

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Diabetic nephropathy is associated with cardiovascular morbidity and mortality [1,2]. It is also associated with increased concentrations of serum total and LDL-cholesterol, triglyceride and apolipoprotein (apo)B [3,4,5,6]. In macroalbuminuria HDL-cholesterol is reduced but in microalbuminuric patients HDL-cholesterol has been reported to be reduced [3,4], unchanged [7,8] Abstract Aims/hypothesis. To examine whether the HDL-cholesterol:apoA-I + apoA-II ratio and the e2 allele are related to albuminuria at baseline and whether they are risk factors for progression of albuminuria in a cohort study of patients with Type I (insulin-dependent) diabetes mellitus. Methods. At baseline, the study cohort comprised 617 patients, aged 15±60 years, from seven European diabetic centres of the EURODIAB study. Albumin excretion rate, measured in a central laboratory, was categorised as normoalbuminuria at 20 mg/min or less, microalbuminuria between 20 and 200 mg/min or macroalbuminuria at 200 mg/min or over. Of the 250 patients who were normoalbuminuric at baseline and had follow-up albuminuria measurements, 34 patients were defined as early progressors. Results. At baseline, the mean HDL-cholesterol:apoA-I + apoA-II ratio was lower in macroalbuminuric patients (0.79, 95 % CI:0.74±0.83) compared with normoalbuminuric (0.88, 95 % CI:0.87±0.90) patients (p = 0.0002, adjusted for age and sex). At follow-up, 34 patients who progressed from normoalbuminuria to microalbuminuria or macroalbuminuria also had a slightly lower baseline ratio (0.85, 95 % CI:0.80±0.89) than those 216 who remained normoalbuminuric (0.89, 95 % CI:0.87±0.92) (adjusted p = 0.08). Neither of these relations were independent of LDL-cholesterol or fasting triglyceride. There was no association of the e2 allele with albuminuria either at baseline (OR = 1.4, 95 % CI:0.7±2.8) or with progression of albuminuria (OR = 0.4, 95 % CI:0.1±3.5). Conclusion/interpretation. There is an inverse relation of HDL-cholesterol:apoA-I + apoA-II ratio with albuminuria at baseline. This lower ratio in microalbuminuric or macroalbuminuric patients could contribute to the increased risk of cardiovascular disease associated with nephropathy. There is weak evidence that HDL-composition is a risk factor for progression of albuminuria and no association of the e2 allele with diabetic nephropathy. [Diabetologia 2000

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“…These raised the possibility that the ε2 allele increased the risk of DN in Chinese, Japanese and Korean patients with T2DM [7][8][9]. However, additional few studies in East Asian populations conflicted with this result [10].…”

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The apolipoprotein E (APOE) gene and the risk of diabetic nephropathy (DN): a meta-analysis in East Asian populations

Feng

Zhu

et al. 2010

Asian Biomedicine

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Background: Several studies have examined the association between DN and the APOE gene, but the results have been inconsistent. Objective: Determine whether APOE is a risk factor for DN by a meta-analysis. Methods: A meta-analysis was performed using all findings of 16 similar case-control studies in East Asian to evaluate the effect of APOE as a risk factor for DN. Several electronic databases were searched for relevant articles up to 2009. After data collection, a meta-analysis was used to assess heterogeneity, combine results and evaluate variations by using software STATA SE 9.0. Publication bias was examined by the Egger's linear regression test and fail-safe number. Conclusion:The ε2 allele conferred a higher risk of DN in East Asians, and no significant result was obtained with the ε4 allele.

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Apolipoprotein E2, renal failure and lipid abnormalities in non-insulin-dependent diabetes mellitus

Cited by 48 publications

References 36 publications

APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes

APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes

Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients

The apolipoprotein E (APOE) gene and the risk of diabetic nephropathy (DN): a meta-analysis in East Asian populations

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