A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.
A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.
复制标题
DOI：
10.1016/j.numecd.2011.01.006
复制
发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Sanghera DK
中科院分区：
文献类型：
--
作者：
Been LF;Hatfield JL;Shankar A;Aston CE;Ralhan S;Wander GS;Mehra NK;Singh JR;Mulvihill JJ;Sanghera DK
在最近的全基因组关联研究（GWAS）中，MTNR 1B中的两种常见变体（rs 1387153，rs 10830963）已被报道对空腹血糖（FBG）水平具有独立影响，并增加了2型糖尿病（T2 D）的风险。在这项研究中，我们报告了这两个变异体，以及MTNR 1 B的GWAS基因座内的另一个变异体（rs 1374645）与来自印度的亚洲锡克教徒样本中的FBG、2小时葡萄糖、胰岛素抵抗（HOMA IR）、β细胞功能（HOMA B）和T2 D的相关性。我们的队列包括2，222例受试者[1，201例T2 D，1，021例对照]。这些SNP均与该队列中的T2 D无关。我们的数据也不能证实rs 1387153和rs 10830963与FBG表型的关联。然而，根据体重指数（BMI）对数据进行分层后，血糖正常受试者（低血糖≤ 25 kg/m2，高血糖> 25 kg/m2）（n= 1，021），rs 1374645显示与低BMI组的低FBG水平有很强的相关性（β=-0.073，p=0.002，Bonferoni p= 0.01）与高BMI组（β= 0.015，p=0.50）相比。我们还发现了rs 1374645和BMI之间在FBG水平方面相互作用的强有力证据（p= 0.002）。我们的数据提供了关于另一种MTNR 1B变体对FBG水平的显著影响的新信息，这种影响似乎受到BMI的调节。未来需要对独立数据集和功能研究进行确认，以确定该变体在空腹血糖变化中的作用。
Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), β-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2,222 subjects [1,201 T2D, 1,021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ≤ 25 kg/m2 and high > 25 kg/m2) in normo-glycemic subjects (n= 1,021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (β= −0.073, p=0.002, Bonferoni p= 0.01) compared to the high BMI group (β= 0.015, p=0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p= 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.
登录
查看更多内容
影响因子：
--
作者：
Cauchi S;Nead KT;Choquet H;Horber F;Potoczna N;Balkau B;Marre M;Charpentier G;Froguel P;Meyre D
通讯作者：
Meyre D
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Prokopenko I;Langenberg C;Florez JC;Saxena R;Soranzo N;Thorleifsson G;Loos RJ;Manning AK;Jackson AU;Aulchenko Y;Potter SC;Erdos MR;Sanna S;Hottenga JJ;Wheeler E;Kaakinen M;Lyssenko V;Chen WM;Ahmadi K;Beckmann JS;Bergman RN;Bochud M;Bonnycastle LL;Buchanan TA;Cao A;Cervino A;Coin L;Collins FS;Crisponi L;de Geus EJ;Dehghan A;Deloukas P;Doney AS;Elliott P;Freimer N;Gateva V;Herder C;Hofman A;Hughes TE;Hunt S;Illig T;Inouye M;Isomaa B;Johnson T;Kong A;Krestyaninova M;Kuusisto J;Laakso M;Lim N;Lindblad U;Lindgren CM;McCann OT;Mohlke KL;Morris AD;Naitza S;Orrù M;Palmer CN;Pouta A;Randall J;Rathmann W;Saramies J;Scheet P;Scott LJ;Scuteri A;Sharp S;Sijbrands E;Smit JH;Song K;Steinthorsdottir V;Stringham HM;Tuomi T;Tuomilehto J;Uitterlinden AG;Voight BF;Waterworth D;Wichmann HE;Willemsen G;Witteman JC;Yuan X;Zhao JH;Zeggini E;Schlessinger D;Sandhu M;Boomsma DI;Uda M;Spector TD;Penninx BW;Altshuler D;Vollenweider P;Jarvelin MR;Lakatta E;Waeber G;Fox CS;Peltonen L;Groop LC;Mooser V;Cupples LA;Thorsteinsdottir U;Boehnke M;Barroso I;Van Duijn C;Dupuis J;Watanabe RM;Stefansson K;McCarthy MI;Wareham NJ;Meigs JB;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
30.8
作者：
Bouatia-Naji, Nabila;Bonnefond, Amelie;Froguel, Philippe
通讯作者：
Froguel, Philippe
影响因子：
30.8
作者：
Lyssenko, Valeriya;Nagorny, Cecilia L. F.;Erdos, Michael R.;Wierup, Nils;Jonsson, Anna;Spegel, Peter;Bugliani, Marco;Saxena, Richa;Fex, Malin;Pulizzi, Nicolo;Isomaa, Bo;Tuomi, Tiinamaija;Nilsson, Peter;Kuusisto, Johanna;Tuomilehto, Jaakko;Boehnke, Michael;Altshuler, David;Sundler, Frank;Eriksson, Johan G.;Jackson, Anne U.;Laakso, Markku;Marchetti, Piero;Watanabe, Richard M.;Mulder, Hindrik;Groop, Leif
通讯作者：
Groop, Leif