The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

Li, Tingting; Shi, Yunying; Yin, Jieyun; Qin, Qin; Wei, Sheng; Nie, Shaoping; Liu, Li

doi:10.1007/s11255-014-0843-6

Cited by 18 publications

(11 citation statements)

References 51 publications

(68 reference statements)

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“…It is the authors’ opinion that different ethnic origins may have different effects on the correlation between PPARG Pro12Ala and CKD. Our study found that there was no significant correlation between PPARG Pro12Ala and CKD in the Caucasian sample, whereas results in previous meta-analyses indicated that the PPARG Pro12Ala dominant model has a significant protective effect against CKD [ 32 , 33 , 34 , 37 , 38 , 39 ]. One possible explanation for this is that our study excluded publications with incomplete genetic information, and precisely these excluded studies suggested that PPARG Pro12Ala has a significant protective effect against CKD ( Table 1 ).…”

Section: Discussioncontrasting

confidence: 96%

“…In addition, our case-control study found that there is no significant correlation between PPARG Pro12Ala and ESRD; this is consistent with the findings published in most previous observations pertaining to Asian populations [ 27 , 38 , 44 , 45 , 63 , 64 , 65 , 66 ]. To emphasize the level of evidence, our meta-analysis also indicated no significant correlation between PPARG Pro12Ala and CKD in the Asian sample; this was consistent with the results of previous meta-analyses for Asians [ 33 , 34 , 36 , 37 , 38 ]. However, no definite conclusions could be made from previous meta-analyses for Asians; therefore, TSA was used on our study to determine whether a definite conclusion can be obtained [ 67 ].…”

Section: Discussionsupporting

confidence: 90%

“…Earlier meta-analyses examining the relationship between PPARG Pro12Ala and CKD found that the G/G and G/C genotypes are protective factors against CKD [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. However, no definite conclusion can be drawn based on these meta-analyses [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ] because (1) previous meta-analyses assumed a dominant model (G/G or G/C genotype compared with the C/C genotype), although it is still not proven that the model is the most appropriate inheritance mode for Pro12Ala and (2) artificial errors may occur when the model selection for combining data is based on the degree of heterogeneity [ 40 ]. In addition, there are new studies published after 2013 (including 2321 patients) that have not been included in any meta-analysis [ 41 , 42 , 43 , 44 , 45 , 46 ]; hence, the existing meta-analyses are unable to provide a definite conclusion based on current evidence.…”

Section: Introductionmentioning

confidence: 99%

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PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study—A Key for Reaching Null Association

Chen

Sung

et al. 2020

Genes

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Background: So far, numerous meta-analyses have been published regarding the correlation between peroxisome proliferator-activated receptor gamma (PPARG) proline 12 alanine (Pro12Ala) gene polymorphism and chronic kidney disease (CKD); however, the results appear to be contradictory. Hence, this study is formulated with the objective of using existing meta-analysis data together with our research population to study the correlation between PPARG Pro12Ala gene polymorphism and CKD and evaluate whether an accurate result can be obtained. Methods: First, literature related to CKD and PPARG Pro12Ala available on the PubMed and EMBASE databases up to December 2016 was gathered from 20 publications. Then, the gathered results were combined with our case-control study of 1693 enrolled subjects and a trial sequential analysis (TSA) was performed to verify existing evidence and determine whether a firm conclusion can be drawn. Results: The TSA results showed that the cumulative sample size for the Asian sample was 6078 and was sufficient to support a definite result. The results of this study confirmed that there is no obvious correlation between PPARG Pro12Ala and CKD for Asians (OR = 0.82 (95% CI = 0.66–1.02), I2 = 63.1%), but this was not confirmed for Caucasians. Furthermore, the case-control sample in our study was shown to be the key for reaching this conclusion. Conclusions: The meta-analysis results of this study suggest no significant correlation between PPARG Pro12Ala gene polymorphism and CKD for Asians after adding our samples, but not for Caucasian.

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Section: Discussioncontrasting

confidence: 96%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study—A Key for Reaching Null Association

Chen

Sung

et al. 2020

Genes

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“…Researchers have found the strongest associations in Asian [9], including Chinese [8], and Caucasian populations by case-control studies [8, 9]. In a recent meta-analysis, Li et al [10] concluded that the T allele increases the susceptibility to T2DN. Functional in vitro studies have revealed that the activity of a DNA fragment containing rs2268388 was dramatically increased in proximal tubular epithelial cells (RPTECs), especially in T allele carriers [8].…”

Section: Lipid Metabolism-related Genesmentioning

confidence: 99%

The Susceptibility Genes in Diabetic Nephropathy

Wei

Xiao

et al. 2018

Kidney Dis

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Background: Diabetes mellitus (DM) poses a severe threat to global public health. Diabetic nephropathy (DN) is one of the most common complications of diabetes and the leading cause of end-stage renal disease (ESRD). Approximately 30–40% of DM patients in the world progress to ESRD, which emphasizes the effect of genetic factors on DN. Family clustering also supports the important role of hereditary factors in DN and ESRD. Therefore, a large number of genetic studies have been carried out to identify susceptibility genes in different diabetic cohorts. Extensive susceptibility genes of DN and ESRD have not been identified until recently. Summary and Key Messages: Some of these associated genes function as pivotal regulators in the pathogenesis of DN, such as those related to glycometabolism and lipid metabolism. However, the functions of most of these genes remain unclear. In this article, we review several susceptibility genes according to their genetic functions to make it easier to determine their exact effect on DN and to provide a better understanding of the advancements from genetic studies. However, several challenges associated with investigating the genetic factors of DN still exist. For instance, it is difficult to determine whether these variants affect the expression of the protein they encode or other cytokines. More efforts should be made to determine how these genes influence the progression of DN. In addition, many results could not be replicated among races, suggesting that the association between genetic polymorphisms and DN is race-specific. Therefore, large, well-designed studies involving more relevant variables and ethnic groups and more relevant functional studies are urgently needed. These studies may be beneficial and retard the progression of DN by early intervention, especially for patients who carry certain risk alleles or genotypes.

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“… 39 The rs1801282 C>G variant in PPARγ was closely associated with decreased DN risk. 40 However, further studies revealed that the PPARγ2 Ala12 variant provided renal protection by reducing the occurrence of albuminuria among patients with type 2 diabetes. 41 , 42 …”

Section: Nuclear Receptorsmentioning

confidence: 99%

ISN Forefronts Symposium 2015: Nuclear Receptors and Diabetic Nephropathy

Zheng

Chen

Gonzalez

2016

Kidney International Reports

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Diabetic nephropathy (DN) is the major reason for end stage renal disease in the western world. Patients with DN developed more severe cardiovascular complications with worse prognosis. In spite of tight blood pressure and glucose control through applying angiotensin II receptor antagonism, angiotensin receptor inhibitors and even direct renin inhibitors, the progression and development of DN has continued to accelerate. Nuclear receptors are, with few exceptions, ligand-depended transcription factors some of which modulate genes involved in the transportation and metabolism of carbohydrate or lipid, and inflammation. Considering the diverse biological functions of nuclear receptors, efforts have been made to explore their contributions to the pathogenesis of DN and potential therapeutic strategies. This review is mainly focused on the association between various nuclear receptors and the pathogenesis of DN, the potential beneficial effects of targeting these receptors for preventing the progress of DN, and the important role that nuclear receptors may play in future therapeutic strategies for DN.

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The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

Abstract: Our meta-analysis supports that the ApoE ε2 allele and ACACB rs2268388 C>T might act as promotion factors of nephropathy in type 2 diabetes, whereas PPARγ rs1801282 C>G is a promising candidate genetic variation for reducing susceptibility to T2DN.

Cited by 18 publications

References 51 publications

PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study—A Key for Reaching Null Association

PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study—A Key for Reaching Null Association

The Susceptibility Genes in Diabetic Nephropathy

ISN Forefronts Symposium 2015: Nuclear Receptors and Diabetic Nephropathy

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