The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.
The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.
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DOI：
10.1007/s12263-015-0454-6
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发表时间：
2015-03
影响因子：
3.5
通讯作者：
Gorska, Maria
中科院分区：
文献类型：
--
作者：
Kretowski, Adam;Adamska, Edyta;Maliszewska, Katarzyna;Wawrusiewicz-Kurylonek, Natalia;Citko, Anna;Goscik, Joanna;Bauer, Witold;Wilk, Juliusz;Golonko, Anna;Waszczeniuk, Magdalena;Lipinska, Danuta;Hryniewicka, Justyna;Niemira, Magdalena;Paczkowska, Magdalena;Ciborowski, Michal;Gorska, Maria
大规模全基因组关联研究的荟萃分析最近证实，PROX1基因rs340874单核苷酸多态性与空腹血糖和2型糖尿病有关，但这种联系的机制尚未完全确定。我们研究的目的是评估与rs340874 PROX1变异相关的功能/表型差异。研究小组包括945名来自波兰的受试者(包括634名患有BMI和GT；的25名受试者)，此前没有已知的血糖异常。我们分析了标准化膳食后和口服葡萄糖耐量试验期间的行为模式(饮食、体力活动)、体脂分布和葡萄糖/脂肪代谢。结果发现，携带rs340874PROX1CC基因携带者的高脂餐后非酯化脂肪酸水平较高(p=0.035)，高碳水化合物餐后葡萄糖氧化水平较低(p=0.014)。此外，在CC变异的受试者中，我们发现内脏脂肪积累较高(P<0.001)，但每日食物消耗量却令人惊讶地低(P<0.05)。我们推测，PROX1CC基因型受试者的脂代谢改变可能是糖负荷后血糖水平升高的主要原因，因为脂肪酸可以通过减少碳水化合物的氧化来抑制胰岛素刺激的葡萄糖摄取。我们的观察表明，PROX1变异体在疾病途径上具有多效性，似乎是预防肥胖症和2型糖尿病研究的一个非常有趣的目标。这项研究可能有助于了解内脏肥胖和2型糖尿病风险发展的机制。
Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.
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影响因子：
30.8
作者：
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium;Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium;South Asian Type 2 Diabetes (SAT2D) Consortium;Mexican American Type 2 Diabetes (MAT2D) Consortium;Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium;Mahajan A;Go MJ;Zhang W;Below JE;Gaulton KJ;Ferreira T;Horikoshi M;Johnson AD;Ng MC;Prokopenko I;Saleheen D;Wang X;Zeggini E;Abecasis GR;Adair LS;Almgren P;Atalay M;Aung T;Baldassarre D;Balkau B;Bao Y;Barnett AH;Barroso I;Basit A;Been LF;Beilby J;Bell GI;Benediktsson R;Bergman RN;Boehm BO;Boerwinkle E;Bonnycastle LL;Burtt N;Cai Q;Campbell H;Carey J;Cauchi S;Caulfield M;Chan JC;Chang LC;Chang TJ;Chang YC;Charpentier G;Chen CH;Chen H;Chen YT;Chia KS;Chidambaram M;Chines PS;Cho NH;Cho YM;Chuang LM;Collins FS;Cornelis MC;Couper DJ;Crenshaw AT;van Dam RM;Danesh J;Das D;de Faire U;Dedoussis G;Deloukas P;Dimas AS;Dina C;Doney AS;Donnelly PJ;Dorkhan M;van Duijn C;Dupuis J;Edkins S;Elliott P;Emilsson V;Erbel R;Eriksson JG;Escobedo J;Esko T;Eury E;Florez JC;Fontanillas P;Forouhi NG;Forsen T;Fox C;Fraser RM;Frayling TM;Froguel P;Frossard P;Gao Y;Gertow K;Gieger C;Gigante B;Grallert H;Grant GB;Grrop LC;Groves CJ;Grundberg E;Guiducci C;Hamsten A;Han BG;Hara K;Hassanali N;Hattersley AT;Hayward C;Hedman AK;Herder C;Hofman A;Holmen OL;Hovingh K;Hreidarsson AB;Hu C;Hu FB;Hui J;Humphries SE;Hunt SE;Hunter DJ;Hveem K;Hydrie ZI;Ikegami H;Illig T;Ingelsson E;Islam M;Isomaa B;Jackson AU;Jafar T;James A;Jia W;Jöckel KH;Jonsson A;Jowett JB;Kadowaki T;Kang HM;Kanoni S;Kao WH;Kathiresan S;Kato N;Katulanda P;Keinanen-Kiukaanniemi KM;Kelly AM;Khan H;Khaw KT;Khor CC;Kim HL;Kim S;Kim YJ;Kinnunen L;Klopp N;Kong A;Korpi-Hyövälti E;Kowlessur S;Kraft P;Kravic J;Kristensen MM;Krithika S;Kumar A;Kumate J;Kuusisto J;Kwak SH;Laakso M;Lagou V;Lakka TA;Langenberg C;Langford C;Lawrence R;Leander K;Lee JM;Lee NR;Li M;Li X;Li Y;Liang J;Liju S;Lim WY;Lind L;Lindgren CM;Lindholm E;Liu CT;Liu JJ;Lobbens S;Long J;Loos RJ;Lu W;Luan J;Lyssenko V;Ma RC;Maeda S;Mägi R;Männisto S;Matthews DR;Meigs JB;Melander O;Metspalu A;Meyer J;Mirza G;Mihailov E;Moebus S;Mohan V;Mohlke KL;Morris AD;Mühleisen TW;Müller-Nurasyid M;Musk B;Nakamura J;Nakashima E;Navarro P;Ng PK;Nica AC;Nilsson PM;Njølstad I;Nöthen MM;Ohnaka K;Ong TH;Owen KR;Palmer CN;Pankow JS;Park KS;Parkin M;Pechlivanis S;Pedersen NL;Peltonen L;Perry JR;Peters A;Pinidiyapathirage JM;Platou CG;Potter S;Price JF;Qi L;Radha V;Rallidis L;Rasheed A;Rathman W;Rauramaa R;Raychaudhuri S;Rayner NW;Rees SD;Rehnberg E;Ripatti S;Robertson N;Roden M;Rossin EJ;Rudan I;Rybin D;Saaristo TE;Salomaa V;Saltevo J;Samuel M;Sanghera DK;Saramies J;Scott J;Scott LJ;Scott RA;Segrè AV;Sehmi J;Sennblad B;Shah N;Shah S;Shera AS;Shu XO;Shuldiner AR;Sigurđsson G;Sijbrands E;Silveira A;Sim X;Sivapalaratnam S;Small KS;So WY;Stančáková A;Stefansson K;Steinbach G;Steinthorsdottir V;Stirrups K;Strawbridge RJ;Stringham HM;Sun Q;Suo C;Syvänen AC;Takayanagi R;Takeuchi F;Tay WT;Teslovich TM;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tikkanen E;Trakalo J;Tremoli E;Trip MD;Tsai FJ;Tuomi T;Tuomilehto J;Uitterlinden AG;Valladares-Salgado A;Vedantam S;Veglia F;Voight BF;Wang C;Wareham NJ;Wennauer R;Wickremasinghe AR;Wilsgaard T;Wilson JF;Wiltshire S;Winckler W;Wong TY;Wood AR;Wu JY;Wu Y;Yamamoto K;Yamauchi T;Yang M;Yengo L;Yokota M;Young R;Zabaneh D;Zhang F;Zhang R;Zheng W;Zimmet PZ;Altshuler D;Bowden DW;Cho YS;Cox NJ;Cruz M;Hanis CL;Kooner J;Lee JY;Seielstad M;Teo YY;Boehnke M;Parra EJ;Chambers JC;Tai ES;McCarthy MI;Morris AP
通讯作者：
Morris AP
影响因子：
7.7
作者：
Barker A;Sharp SJ;Timpson NJ;Bouatia-Naji N;Warrington NM;Kanoni S;Beilin LJ;Brage S;Deloukas P;Evans DM;Grontved A;Hassanali N;Lawlor DA;Lecoeur C;Loos RJ;Lye SJ;McCarthy MI;Mori TA;Ndiaye NC;Newnham JP;Ntalla I;Pennell CE;St Pourcain B;Prokopenko I;Ring SM;Sattar N;Visvikis-Siest S;Dedoussis GV;Palmer LJ;Froguel P;Smith GD;Ekelund U;Wareham NJ;Langenberg C
通讯作者：
Langenberg C
影响因子：
5.2
作者：
Jetten AM;Kang HS;Takeda Y
通讯作者：
Takeda Y
影响因子：
5.3
作者：
Hayhurst, GP;Lee, YH;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
16.2
作者：
BIRKELAND, KI;TORJESEN, PA;GROOP, L
通讯作者：
GROOP, L