PPAR 同工型的靶基因变异可能导致 MODY 的异质性：与 2 型糖尿病的初步比较研究。

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2024-11-17 DOI:10.1016/j.diabres.2024.111932

Hulya Yilmaz-Aydogan , Deniz Kanca-Demirci , Nurdan Gul , Cagatay Aydogan , Sukran Poyrazoglu , Yıldız Tutuncu , Fidan Malikova , Oguz Ozturk , Ilhan Satman

{"title":"PPAR 同工型的靶基因变异可能导致 MODY 的异质性：与 2 型糖尿病的初步比较研究。","authors":"Hulya Yilmaz-Aydogan , Deniz Kanca-Demirci , Nurdan Gul , Cagatay Aydogan , Sukran Poyrazoglu , Yıldız Tutuncu , Fidan Malikova , Oguz Ozturk , Ilhan Satman","doi":"10.1016/j.diabres.2024.111932","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>The objective of this study was to evaluate the associations of several genetic variants of peroxisome proliferator-activated receptors (PPARs) on clinical and laboratory parameters in patients with maturity-onset diabetes of the young (MODY), and possible contribution to heterogeneity of the disease.</div></div><div><h3>Methods</h3><div>The study groups comprised patients with MODY (genetically confirmed (n = 28), clinically relevant but genetically unconfirmed; MODYX (n = 56)), type 2 diabetes mellitus (T2DM; n = 94) and healthy controls (n = 153). <em>PPARA</em>-L162V-(rs1800206), <em>PPARG-</em>C161T-(rs3856806), P12A-(rs1801282), and <em>PPARB/D</em> + 294 T/C-(rs2016520) polymorphisms were genotyped by real-time-PCR.</div></div><div><h3>Results</h3><div>The results demonstrated that the frequencies of <em>PPARA</em>-LL162 (p = 0.002), <em>PPARG-</em>CC161 (p = 0.002), and <em>PPARG-</em>ProPro (p = 0.012) genotypes were significantly higher in the MODY group compared to the controls. Furthermore, total-MODY and MODYX groups had a higher frequency of <em>PPARA</em>-LL162 genotype than T2DM (p = 0.005 and p = 0.006, respectively). The frequency of the <em>PPARB/D</em> + 294 T allele was significantly higher in individuals with T2DM than in genetically-determined MODY group (p = 0.019). The <em>PPARA</em>-LL162 genotype was associated with early-onset diabetes in total-MODY (p = 0.022) and T2DM (p < 0.05) groups.</div></div><div><h3>Conclusions</h3><div>The association of <em>PPARA</em>-L162V polymorphism with early-onset diabetes in both T2DM and MODY is a noteworthy finding. Considering these results, we suggested that genetic polymorphisms in <em>PPAR</em> isoforms may contribute to the clinical and metabolic heterogeneity of MODY.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"218 ","pages":"Article 111932"},"PeriodicalIF":6.1000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Target gene variations of PPAR isoforms may contribute to MODY heterogeneity: A preliminary comparative study with type 2 diabetes\",\"authors\":\"Hulya Yilmaz-Aydogan , Deniz Kanca-Demirci , Nurdan Gul , Cagatay Aydogan , Sukran Poyrazoglu , Yıldız Tutuncu , Fidan Malikova , Oguz Ozturk , Ilhan Satman\",\"doi\":\"10.1016/j.diabres.2024.111932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>The objective of this study was to evaluate the associations of several genetic variants of peroxisome proliferator-activated receptors (PPARs) on clinical and laboratory parameters in patients with maturity-onset diabetes of the young (MODY), and possible contribution to heterogeneity of the disease.</div></div><div><h3>Methods</h3><div>The study groups comprised patients with MODY (genetically confirmed (n = 28), clinically relevant but genetically unconfirmed; MODYX (n = 56)), type 2 diabetes mellitus (T2DM; n = 94) and healthy controls (n = 153). <em>PPARA</em>-L162V-(rs1800206), <em>PPARG-</em>C161T-(rs3856806), P12A-(rs1801282), and <em>PPARB/D</em> + 294 T/C-(rs2016520) polymorphisms were genotyped by real-time-PCR.</div></div><div><h3>Results</h3><div>The results demonstrated that the frequencies of <em>PPARA</em>-LL162 (p = 0.002), <em>PPARG-</em>CC161 (p = 0.002), and <em>PPARG-</em>ProPro (p = 0.012) genotypes were significantly higher in the MODY group compared to the controls. Furthermore, total-MODY and MODYX groups had a higher frequency of <em>PPARA</em>-LL162 genotype than T2DM (p = 0.005 and p = 0.006, respectively). The frequency of the <em>PPARB/D</em> + 294 T allele was significantly higher in individuals with T2DM than in genetically-determined MODY group (p = 0.019). The <em>PPARA</em>-LL162 genotype was associated with early-onset diabetes in total-MODY (p = 0.022) and T2DM (p < 0.05) groups.</div></div><div><h3>Conclusions</h3><div>The association of <em>PPARA</em>-L162V polymorphism with early-onset diabetes in both T2DM and MODY is a noteworthy finding. Considering these results, we suggested that genetic polymorphisms in <em>PPAR</em> isoforms may contribute to the clinical and metabolic heterogeneity of MODY.</div></div>\",\"PeriodicalId\":11249,\"journal\":{\"name\":\"Diabetes research and clinical practice\",\"volume\":\"218 \",\"pages\":\"Article 111932\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-11-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes research and clinical practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168822724008428\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes research and clinical practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168822724008428","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

摘要

目的：本研究的目的是评估过氧化物酶体增殖激活受体（PPARs）的几种遗传变异与青年成熟型糖尿病（MODY）患者的临床和实验室参数之间的关系，以及对该疾病异质性的可能贡献：研究小组包括MODY患者（基因确证（n = 28）、临床相关但基因未确证；MODYX（n = 56））、2型糖尿病（T2DM；n = 94）和健康对照组（n = 153）。通过 real-time-PCR 对 PPARA-L162V-（rs1800206）、PPARG-C161T-（rs3856806）、P12A-（rs1801282）和 PPARB/D + 294 T/C-（rs2016520）多态性进行了基因分型：结果表明，与对照组相比，MODY组中PPARA-LL162（p = 0.002）、PPARG-CC161（p = 0.002）和PPARG-ProPro（p = 0.012）基因型的频率明显较高。此外，总MODY组和MODYX组的PPARA-LL162基因型频率高于T2DM组（分别为p = 0.005和p = 0.006）。在 T2DM 患者中，PPARB/D + 294 T 等位基因的频率明显高于由基因决定的 MODY 组（p = 0.019）。PPARA-LL162 基因型与总MODY（p = 0.022）和T2DM（p 结论：PPARA-LL162 基因型与早发糖尿病相关：PPARA-L162V 多态性与 T2DM 和 MODY 的早发糖尿病相关，这是一个值得注意的发现。考虑到这些结果，我们认为 PPAR 同工酶的遗传多态性可能导致 MODY 的临床和代谢异质性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Target gene variations of PPAR isoforms may contribute to MODY heterogeneity: A preliminary comparative study with type 2 diabetes

Aims

The objective of this study was to evaluate the associations of several genetic variants of peroxisome proliferator-activated receptors (PPARs) on clinical and laboratory parameters in patients with maturity-onset diabetes of the young (MODY), and possible contribution to heterogeneity of the disease.

Methods

The study groups comprised patients with MODY (genetically confirmed (n = 28), clinically relevant but genetically unconfirmed; MODYX (n = 56)), type 2 diabetes mellitus (T2DM; n = 94) and healthy controls (n = 153). PPARA-L162V-(rs1800206), PPARG-C161T-(rs3856806), P12A-(rs1801282), and PPARB/D + 294 T/C-(rs2016520) polymorphisms were genotyped by real-time-PCR.

Results

The results demonstrated that the frequencies of PPARA-LL162 (p = 0.002), PPARG-CC161 (p = 0.002), and PPARG-ProPro (p = 0.012) genotypes were significantly higher in the MODY group compared to the controls. Furthermore, total-MODY and MODYX groups had a higher frequency of PPARA-LL162 genotype than T2DM (p = 0.005 and p = 0.006, respectively). The frequency of the PPARB/D + 294 T allele was significantly higher in individuals with T2DM than in genetically-determined MODY group (p = 0.019). The PPARA-LL162 genotype was associated with early-onset diabetes in total-MODY (p = 0.022) and T2DM (p < 0.05) groups.

Conclusions

The association of PPARA-L162V polymorphism with early-onset diabetes in both T2DM and MODY is a noteworthy finding. Considering these results, we suggested that genetic polymorphisms in PPAR isoforms may contribute to the clinical and metabolic heterogeneity of MODY.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.