PPP1R3基因3′端非翻译区5 bp缺失/插入多态性与2型糖尿病相关性研究

目的　研究 1型蛋白磷酸酶骨骼肌特异糖原靶向调节亚单位 (PPP1R3)基因 3′-非翻译区 5 bp缺失 /插入 (deletion/insertion,D/I)多态性与 2型糖尿病 (type 2 diabetes,T2 DM)的相关性。方法　选取安徽省合肥地区汉族 T2 DM患者 2 6 8例 ,正常对照 10 6名 ,用聚合酶链反应扩增片段长度多态性技术进行基因型测定。结果　 (1) PPP1R3基因 3′-非翻译区 5 bp D/I多态性的基因型及等位基因频率在 T2 DM与正常对照组间分布差异无显著性 (P>0 .0 5 )。(2 ) T2 DM或正常对照组中不同基因型间发病年龄、病程、空腹血糖、餐后 2 h血糖、空腹胰岛素、胰岛素敏感指数、体重指数、腰臀围比、收缩压、舒张压差异均无显著性 (P>0 .0 5 )。(3) PPP1R3基因 3′-非翻译区 5 bp D/I多态性频率与日本人群和加拿大人群相近。明显低于 Pima印第安人、瑞典的白人。结论　 PPP1R3基因 3′-非翻译区 5 bp D/I多态性与安徽省合肥地区 2型糖尿病发病无明显关联 ,具有明显的种族差异。     

等位基因3′末端碱基特异性引物定量PCR检测人脂联素基因单核苷酸多态性

目的建立非探针标记荧光定量PCR的SNP检测技术,分析人脂联素(APM1)基因单核苷酸多态性(SNP)与Ⅱ型糖尿病(T2DM)的关系。方法设计3′末端碱基特异性引物,进行定量PCR反应,通过比较各对引物的扩增效率判断基因型,并进行测序验证。利用该方法确定20例T2DM、24例肥胖及28例同年龄组正常人APM1基因的45位和276位碱基的SNP。结果该方法能有效地区分不同的基因型,与测序结果符合率100%。APM1基因45位SNP与T2DM相关(P<0.05),基因型为TT纯合子者发生T2DM的危险性是G/T和GG者的3倍;而肥胖与APM1基因45和276位点SNP无关。结论等位基因3′末端碱基特异性引物定量PCR可以用于基因SNP检测。APM1基因45位碱基的SNP与T2DM发生有关。     

配对盒4基因Arg121Trg多态性与2型糖尿病的相关性

目的 探讨配对盒4(Pax4)基因Arg121Trg多态性(rs114202595)与云南省昆明地区2型糖尿病的相关性.方法 根据口服75 g葡萄糖耐量试验(OGzTT)将1 076例云南省昆明地区人群分为2型糖尿病组(T2DM)、糖耐量减低组(IGT)和健康对照组(NGT),应用高分辨率熔解曲线分析方法(HRM)检测Pax4基因Arg121Trg基因型,观察3组人群中基因型和等位基因的分布情况,同时分析T2DM人群中不同基因型相关临床变量的差异性.结果 1)Pax4基因Arg121 Trg GG基因型(Arg/Arg)及A等位基因(Trg121)在T2DM组中的频率分别为0.909和0.047,在IGT组中为0.935和0.035,在NGT组中为0.939和0.03.2)T2DM组Arg121Trg 多态性GA+ AA基因型(Arg/Trg+ Trg/Trg)人群胰岛素使用率显著高于GG基因型(Arg/Arg)人群(P=0.001),而其他临床变量在T2DM组中两种基因型人群间比较均无明显差异.结论 Pax4基因Arg121Trg多态性A等位基因可能是云南省昆明地区2型糖尿患者群胰岛β功能进展性紊乱的一个分子标记.     

成都地区汉族人群PPARGC1A基因Thr394Thr位点G/A多态性与2型糖尿病及胰岛素抵抗的相关性研究

目的 了解中国成都地区汉族人群过氧化物酶体增殖物激活受体γ辅助激活因子-1α基因(peroxisome proliferator-activated receptor gamma,coactivator 1 alpha,PPARGC1A;又名PGC-1α)Thr394Thr位核苷酸G/A的基因型分布,探讨该多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)、胰岛素抵抗及其他代谢异常的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术检测151例无亲缘关系的T2DM患者和156名糖耐量正常对照者PPARGC1A基因Thr394Thr位核苷酸G/A多态性.所有研究对象均测定血糖、胰岛素、血脂,测量身高、体重、腰围、血压.结果 与正常对照组相比,T2DM组的体重指数、腰围、血压、甘油三酯水平均显著增高(P＜0.05),而高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)水平显著降低(P＜0.05).A等位基因的频率在T2DM及正常对照组分别为22.5%、18.6%,AG基因型频率在两组分别为43.7%、37.2%,差异无统计学意义.在T2DM组中,AA+AG基因型的空腹胰岛素、稳态模型评估法胰岛素抵抗指数(homeostasis model aseessment-insulin resistance,HOMA-IR)及腰围明显高于GG基因型,HDL-C显著低于GG基因型(P＜0.05).无论T2DM和正常对照,A等位基因携带者HOMA-IR明显高于GG者.结论 PPARGC1A基因Thr394Thr位核苷酸G/A多态性与胰岛素抵抗存在明显相关,并可能与T2DM患者中心性肥胖及低HDL-C水平相关,其与T2DM发病的关系有待进一步研究.     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

原发性开角型青光眼患者Myocilin基因的单核苷酸多态性

目的　探讨 Myocilin(MYOC)基因的单核苷酸多态性 (single nucleotide polymorphisms,SNPs)及其与原发性开角型青光眼 (primary open- angle glaucoma,POAG)发病的关系。方法　应用高通量构象敏感性凝胶电泳和荧光标记自动测序法筛选和鉴定香港 15 7例 POAG散发患者和 15 5名对照 MYOC基因的 SNPs。结果　在 MYOC基因所有 3个外显子及邻近的非编码区共检出 17种 SNPs:1- 83G→ A、G12 R、P16 L、A17S、R4 6 X、R76 K、R91X、T12 3T、D2 0 8E、L 2 15 P、730 35 A→ G、A2 6 0 A、I2 88I、E30 0 K、T35 3I、Y4 71C和 15 15 73G→ C。其中 ,R91X、E30 0 K和 Y4 71C仅在 POAG患者中检测到。此外 ,15 15 73G→ C各基因型在 POAG患者与对照人群中的分布差异具有显著意义 ,POAG患者中 CG型频率为 0 .6 % ,低于对照组的 4 .5 % (P=0 .0 36 )。其余 16种 SNPs各基因型在两组人群中的分布差异均无显著意义。结论　 MYOC基因多态性可能与中国人 POAG发病有关 ,提示 MYOC基因是 POAG的相关基因。     

血管紧张素Ⅱ的Ⅰ型受体基因多态性和胰岛素抵抗与2型糖尿病冠心病的关系

目的　探讨血管紧张素Ⅱ的Ⅰ型受体 (typeⅠangiotensinⅡreceptor,AT1R)基因A116 6C多态性和胰岛素抵抗 (insulinresistance ,IR)与 2型糖尿病 (type 2diabetesmellitus,DM2 )冠心病的关系。方法应用PCR -RFLP法 ,对 6 2例DM2合并冠心病 (CHD)患者 ,4 9例DM2 非合并CHD患者和 10 1例正常对照组人群的AT1R基因A116 6C多态性进行检测 ;以 -log(空腹血糖×空腹胰岛素 )作为IR指标。结果　DM2 合并CHD组与DM2 非合并组比较 :AT1R基因型频率的差异无显著性 (P >0 .0 5 ) ;合并CHD组C等位基因频率显著升高 (0 .0 81vs0 .0 2 1) P <0 .0 5 ;OR =4 .2 1,95 %CI :1.0 0— 17.6 0。DM2 合并CHD组与非合并CHD组相比 ,ISI(- 2 .0 1vs- 1.77)显著升高 (P <0 .0 1)。AT1R基因多态性各基因型之间IR指标无显著性差异 (P >0 .0 5 )。结论　AT1R基因A116 6C多态性参与中国汉族人群DM 2CHD的发病 ;AT1R基因A116 6C多态性与IR无相关性 ;AT1R基因 116 6C等位基因携带者不是通过IR的影响而参与DM2 CHD的发病。     

CDKN2A/2B基因多态性与妊娠糖尿病相关

目的研究CDKN2A/2B基因rs10811661的单核苷酸多态性(SNP),探讨其与妊娠糖尿病(GDM)的相关性。方法选取鲁西南地区正常糖耐量孕妇(NGT)100例、GDM患者120例、2型糖尿病(T2DM)患者100例作为研究对象,提取基因组DNA,采用PCR-RFLP方法检测CDKN2A/2B基因rs10811661多态性。结果 CDKN2A/2B基因rs10811661的TT、TC、CC 3种基因型分布在NGT组与GDM组间有显著差别(P<0.01),GDM组危险等位基因T分布频率显著高于NGT组(P<0.05)。3种基因型及等位基因分布在NGT组与T2DM组之间亦有显著差别(P<0.05)。结论在鲁西南地区女性人群中,CDKN2A/2B基因rs10811661 T/C多态性可能与妊娠糖尿病有明显相关性。     

HLA-DRB1等位基因与中国北方地区汉族人2型糖尿病大血管病变的相关性研究

目的 :探讨HLA DRB1基因多态性与 2型糖尿病 (type 2diabetesmellitus,T2DM)大血管病变的关系。方法 :采用序列特异性引物聚合酶链反应技术 (polymerasechainreactionwithsequence specificprimers ,PCR SSP)检测了中国北方地区汉族人88例T2DM患者 ( 5 2例无并发症 ,36例合并大血管病变 )HLA DRB1等位基因多态性。结果 :T2DM患者至少存在 11种HLA DRB1等位基因 ,T2DM伴大血管并发症组HLA DRB1 0 3、HLA DRB1 0 90 12基因频率明显高于无并发症组 (P <0 .0 5 )。结论 :HLA DRB1基因中DRB1 0 3、DRB1 0 90 12等位基因或其连锁不平衡基因可增高T2DM发生大血管并发症的危险性     

PAI-1基因和MTHFR基因多态性与复发性早期自然流产的关系

目的探讨纤溶酶原激活剂抑制物1(plasminogenactivatorinhibitor1,PAI1)基因和亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因多态性与复发性早期自然流产(recurrentearlyspontaneousabortion,RESA)的相关性。方法选取127例RESA非妊娠患者和117名健康非妊娠妇女,应用聚合酶链反应限制性片段长度多态性分析技术检测PAI1基因-675位4G/5G多态性和MTHFR基因C677T位点多态性。结果(1)患者组PAI1基因4G/4G基因型频率(45.7%)和4G等位基因频率(66.1%)显著高于对照组(17.1%和46.6%)(P<0.01),与5G/5G基因型比较,4G/4G型患者发生RESA的相对风险率的比数比(oddsratio,OR)为4.8,95%的可信区间(confidenceinterval,CI):2.23～10.35;(2)MTHFR基因T/T基因型和T等位基因频率患者组(43.3%和66.5%)显著高于正常对照组(21.4%和52.6%)(P<0.01),与C/C基因型比较,T/T型患者发生RESA的相对风险率为OR=3.2,95%CI:1.40～7.30;(3)RESA患者若同时兼有4G/4G和T/T基因型时,发生自然流产的相对风险率明显增加,OR=6.20,95%CI:2.62～14.67。结论PAI1基因4G/5G多态性和MTHFR基因C677T位点多态性与不明原因RESA密切相关,易感基因型4G/4G型和T/T型对RESA的发生具有协同作用。     

全氟化合物与儿童哮喘及Th1/Th2免疫应答平衡相关性研究

目的 采用病例对照探讨全氟化合物(PFAAS)暴露与儿童哮喘及Th1型细胞因子白细胞介素(IL)-2,干扰素(IFN)-γ和Th2型细胞因子(IL-4,IL-5)分泌水平的关系.方法 选择231名台北医院就诊的哮喘儿童作为病例组,来自社区的225名自然儿童作为对照组.采用双抗体酶联免疫吸附实验(ELISA)试剂盒检测儿童血清中细胞因子IL-2、IFN-γ、IL-4和IL-10的分泌水平;高效液相色谱仪分析血清中全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)水平.结果 哮喘儿童机体PFOS(33.9μg/L比28.9 μg/L)和PFOA(1.2μg/L比0.5 μg/L)暴露负荷显著的高于对照组儿童,且随着机体PFAAs的增高,儿童患有哮喘的风险呈增高趋势.对哮喘儿童而言,血清PFAAs水平与Th1型细胞因子(IL-2,IFN-γ)存在显著的负相关,而与Th2型细胞因子(IL-4,IL-5)呈正相关关系.结论 PFOS暴露可诱导机体免疫应答平衡紊乱,并向Th2型免疫应答极化.     

The effects of entorhinal cortex lesions on type 1 and type 2 theta

The effects of bilateral entorhinal cortex lesions on type 1 and type 2 theta generation in the guinea pig were studied in the chronic preparation. EEG recordings from dentate generator zones demonstrated a decrease in the relationship between ongoing type 1 motor movements and theta generation. Before lesioning theta activity accompanied type 1 behaviors (i.e., walking and head movements) in 100% of the samples, while subsequent to lesioning theta activity was present in only 58% of the samples. In addition, prior to lesioning, type 2 theta was present in 100% of the samples taken during immobile sensory processing, e.g., tactile stimulation, while after lesioning type 2 theta was present in only 34% of the samples. Type 2 theta is selectively sensitive to disruption by atropine sulfate. In the present experiment atropine sulfate eliminated all theta activity after entorhinal lesions. Consequently as no type 1 theta appeared to be present it was argued that the entorhinal cortex is a critical route for type 1 theta. However, as the behavioral and sensory correlates of both type 1 and type 2 theta were disrupted it was suggested that the entorhinal cortex is an integral part of both systems.     

PCR－RFLP用于Ⅰ型脊髓灰质炎病毒野毒株与疫苗相关株的鉴别

利用互补于Ⅰ型脊髓灰质炎病毒ＶＰ１区的一对引物，扩增病毒核酸中约２６８ｂｐ的片段。产物经ＨａｅⅢ、ＲｓａⅠ、ＸｂａⅠ三种限制性内切酶切割后，用２％琼脂糖凝胶电泳检测，观察各分离株与ＳａｂｉｎⅠ型株酶切图谱的异同。在所检测的１３株病毒分离株中，只有１株的酶切图谱与ＳａｂｉｎⅠ型株的相同，为疫苗相关株，其它的１２株均为野毒株。本实验的结果表明从不同地区、不同年份所得的Ⅰ型脊髓灰质炎病毒分离株的碱基组成是有差异的。     

Sphingomyelin profiling in patients with diabetes could be potentially useful as differential diagnostics biomarker: A pilot study

PurposeAutoimmune diabetes (AD) in adults includes both the classical form of type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). LADA shares clinical and metabolic features with type 1 and type 2 diabetes mellitus (T2DM). Ceramide (Cer) levels negatively correlate with insulin sensitivity in humans and animal models. However, only a few studies have focused on other sphingolipids, including sphingomyelin (SM). Therefore, we determined sphingolipids in patients with newly diagnosed diabetes as possible diagnostic biomarkers.Materials and methodsWe evaluated sphingolipids in a cohort of 59 adults with newly diagnosed diabetes without prior hypoglycemic pharmacotherapy to distinguish diabetes mellitus types and for precise LADA definition. All patients with newly diagnosed diabetes were tested for the concentrations of individual Cer and SM species by gas-liquid chromatography. The study included healthy controls and patients with T1DM, T2DM and LADA.ResultsSM species were significantly altered in patients with newly diagnosed diabetes compared to healthy controls. SM-C16:0, C16:1, -C18:0, -C18:1, -C18:2, -C18:3, -C20:4, and -C22:6 species were found to be significantly elevated in LADA patients. In contrast, significant differences were observed for Cer species with saturated acyl chains, especially Cer-C14:0, -C16:0, -C18:0 (AD and T2DM), -C22:0, and -C24:0 (T1DM). Following ROC analysis, SM-C16:0, and particularly -C18:1, and -C20:4 may be supportive diagnostic markers for LADA.ConclusionSM profiling in patients with newly diagnosed diabetes could be potentially helpful for differential diagnosis of LADA, T1DM, and T2DM in more challenging cases.     

Reduced IL-2 expression in NOD mice leads to a temporal increase in CD62Llo FoxP3+ CD4+ T cells with limited suppressor activity

IL-2 plays a critical role in the induction and maintenance of FoxP3-expressing regulatory T cells (FoxP3(+) Tregs). Reduced expression of IL-2 is linked to T-cell-mediated autoimmune diseases such as type 1 diabetes (T1D), in which an imbalance between FoxP3(+) Tregs and pathogenic T effectors exists. We investigated the contribution of IL-2 to dysregulation of FoxP3(+) Tregs by comparing wildtype NOD mice with animals congenic for a C57BL/6-derived disease-resistant Il2 allele and in which T-cell secretion of IL-2 is increased (NOD.B6Idd3). Although NOD mice exhibited a progressive decline in the frequency of CD62L(hi) FoxP3(+) Tregs due to an increase in CD62L(lo) FoxP3(+) Tregs, CD62L(hi) FoxP3(+) Tregs were maintained in the pancreatic lymph nodes and islets of NOD.B6Idd3 mice. Notably, the frequency of proliferating CD62L(hi) FoxP3(+) Tregs was elevated in the islets of NOD.B6Idd3 versus NOD mice. Increasing levels of IL-2 in vivo also resulted in larger numbers of CD62L(hi) FoxP3(+) Tregs in NOD mice. These results demonstrate that IL-2 influences the suppressor activity of the FoxP3(+) Tregs pool by regulating the balance between CD62L(lo) and CD62L(hi) FoxP3(+) Tregs. In NOD mice, reduced IL-2 expression leads to an increase in nonsuppressive CD62L(lo) FoxP3(+) Tregs, which in turn correlates with a pool of CD62L(hi) FoxP3(+) Tregs with limited proliferation.     

Tumor necrosis factor-associated susceptibility to type 1 diabetes is caused by linkage disequilibrium with HLA-DR3 haplotypes

Tumor necrosis factor-α (TNF-α) is an important proinflammatory cytokine involved in the pathogenesis of autoimmune type 1 diabetes (T1D). The TNF gene locus is located in the major histocompatibility complex (MHC) class III region and its genetic polymorphisms have been reported to be associated with T1D. However, it is not clear whether these associations are primary or caused by their linkage disequilibrium with other predisposing genes within the MHC. We have tested 2 TNF-α single nucleotide polymorphisms at positions -308G/A and -238G/A in the 5' untranslated region and a (GT)n microsatellite TNFa in the North Indian healthy population and T1D patients with known HLA-A-B-DR-DQ haplotypes. The allele frequencies of TNFa5, -308A, and -238G were determined to be significantly increased among patients compared with controls. Although the observed positive association of -238G was caused by its presence on all 3 DR3(+) groups, namely, B8-DR3-DQ2, B50-DR3-DQ2, and B58-DR3-DQ2 haplotypes associated with T1D in this population, the increase of the -308A allele was caused by its association with the latter 2 haplotypes. On the other hand, TNF -308G occurred on B8-DR3 haplotypes along with -238G and TNFa5 alleles, particularly in T1D patients with late disease onset (at >20 years of age). These results indicate that TNF associations with T1D are caused by their linkage disequilibrium with specific HLA-DR3-DQ2 haplotypes in the Indian population. Because polymorphisms in the promoter region regulate TNF expression levels (e.g., -308A), they retain crucial immunological significance in the development of T1D and its management.     

Short-term IL-1β blockade reduces monocyte CD11b integrin expression in an IL-8 dependent fashion in patients with type 1 diabetes

Objective

Interleukin 1-beta (IL-1β) is a major inflammatory cytokine. Blockade of the IL-1β pathway is therapeutically efficacious in type 2 diabetes, but the mechanistic effects on the immune system are incompletely understood.

Research design

We administered an IL-1 receptor antagonist, anakinra, to 7 type 1 diabetes patients in order to investigate the immunologic and metabolic effects of this drug. Mechanistic assays were performed before and after drug administration.

Results

A novel signature was observed, with reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression.

Conclusions

This set of linked phenotypes suggests that blockade of the IL-1β pathway results in the reduced ability of mononuclear cells to traffic to sites of inflammation. Mechanistic studies from large scale trials using IL-1 blockade in type 1 diabetes should focus on changes in monocyte trafficking and the IL-8 pathway.     

Peripherally induced regulatory T cells contribute to the control of autoimmune diabetes in the NOD mouse model

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3⁺ regulatory T‐cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3⁺ Tregs is generated in the periphery (pTregs) from Foxp3^?CD4⁺ T‐cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobese diabetic (NOD) mouse model for T1D. We generated NOD mice deficient for the Foxp3 enhancer CNS1 involved in pTreg induction. We show that CNS1 knockout decreased the frequency of pTregs and increased the risk of diabetes. Our results show that pTregs fulfill an important non‐redundant function in the prevention of beta cell autoimmunity that causes T1D.     

A disease-specific questionnaire for measuring patient-reported outcomes and experiences in the Swedish National Diabetes Register: Development and evaluation of content validity,face validity,and test-retest reliability

Objective

To describe the development and evaluation of the content and face validity and test-retest reliability of a disease-specific questionnaire that measures patient-reported outcomes and experiences for the Swedish National Diabetes Register for adult patients who have type 1 or type 2 diabetes.

Genetic Variation in the Peroxisome Proliferator‐Activated Receptor (PPAR) and Peroxisome Proliferator‐Activated Receptor Gamma Co‐activator 1 (PGC1) Gene Families and Type 2 Diabetes

We used a two‐stage study design to evaluate whether variations in the peroxisome proliferator‐activated receptors (PPAR) and the PPAR gamma co‐activator 1 (PGC1) gene families (PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B) are associated with type 2 diabetes (T2D) risk. Stage I used data from a genome‐wide association study (GWAS) from Shanghai, China (1019 T2D cases and 1709 controls) and from a meta‐analysis of data from the Asian Genetic Epidemiology Network for T2D (AGEN‐T2D). Criteria for selection of single nucleotide polymorphisms (SNPs) for stage II were: (1) P < 0.05 in single marker analysis in Shanghai GWAS and P < 0.05 in the meta‐analysis or (2) P < 10^?3 in the meta‐analysis alone and (3) minor allele frequency ≥ 0.10. Nine SNPs from the PGC1 family were assessed in stage II (an independent set of middle‐aged men and women from Shanghai with 1700 T2D cases and 1647 controls). One SNP in PPARGC1B, rs251464, was replicated in stage II (OR = 0.87; 95% CI: 0.77–0.99). Gene‐body mass index (BMI) and gene–exercise interactions and T2D risk were evaluated in a combined dataset (Shanghai GWAS and stage II data: 2719 cases and 3356 controls). One SNP in PPARGC1A, rs12640088, had a significant interaction with BMI. No interactions between the PPARGC1B gene and BMI or exercise were observed.