儿童哮喘与肥胖的共同性遗传因素分析
2010/11/04
摘要
背景：流行病学研究一致显示，哮喘与肥胖存在着相关性，这可能与肥胖与哮喘存在共同性遗传特征有关。
目的：本文旨在研究与哮喘和肥胖相关的遗传变异。
方法：基于文献检索，从下列研究中寻找相关基因：(1)体重指数（BMI）相关基因组研究（GWASs）(n = 17 genes)；(2)哮喘的GWASs（n = 14）；(3)BMI和哮喘的候选基因研究（n = 7）。我们采用儿童哮喘管理项目的GWAS数据分析这些基因的单核苷酸多态性（SNPs）与哮喘（n=359）及BMI（n=537）之间的关系。
结果：一项有关BMI与GWAS SNP的研究显示，靠近氨基葡萄糖- 6 -磷酸脱氨酶（GNPDA2）的rs10938397与BMI（P = 4 x 10-4）和哮喘（P =0.03）相关。有关哮喘GWAS SNPs及候选基因SNPs的研究，并未发现BMI与哮喘的相关性。基于基因的分析包括了所有基因的SNPs，结果显示与某些基因的表型有关（P <0.05）。与BMI相关的基因包括：神经生长调节子（NEGR1）、环岛-轴突导向受体-同源物1（ROBO1）、甘油二酯激酶γ（DGKG）、Fas凋亡抑制分子（FAIM2）、脂肪量与肥胖相关基因（FTO）、碳水化合物（N-乙酰氨基4-0）磺基转移酶8（CHST8）；与哮喘相关基因包括：白介素1受体样1/白介素18受体1（IL1RL1/IL18R1）、二肽基肽酶10（DPP10）、磷酸二酯酶4D（PDE4D）、V-myb原粒细胞增多症病毒癌基因同源物（MYB）、PDE10A、IL33、D型蛋白酪氨酸磷酸酶受体（PTPRD）；哮喘和BMI候选基因包括：蛋白激酶Ca（PRKCA）。
结论：一些基因的SNPs显示在遗传水平上与BMI和哮喘都存在相关性，但经过多次测试校正后这些相关性并不显著。对已知的候选基因进行分析表明，有证据显示哮喘与肥胖之间存在遗传学相关性，但有必要寻找其他新的遗传决定因素。
（林江涛 审校）
J Allergy Clin Immunol. 2010 Sep;126(3):631-7.e1-8.
Analyses of shared genetic factors between asthma and obesity in children.
Melén E, Himes BE, Brehm JM, Boutaoui N, Klanderman BJ, Sylvia JS, Lasky-Su J.
Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass 02115, USA. erik.melen@ki.se
Abstract
BACKGROUND: Epidemiologic studies consistently show associations between asthma and obesity. Shared genetics might account for this association.
OBJECTIVE: We sought to identify genetic variants associated with both asthma and obesity.
METHODS: On the basis of a literature search, we identified genes from (1) genome-wide association studies (GWASs) of body mass index (BMI; n = 17 genes), (2) GWASs of asthma (n = 14), and (3) candidate gene studies of BMI and asthma (n = 7). We used GWAS data from the Childhood Asthma Management Program to analyze associations between single nucleotide polymorphisms (SNPs) in these genes and asthma (n = 359 subjects) and BMI (n = 537).
RESULTS: One top BMI GWAS SNP from the literature, rs10938397 near glucosamine-6-phosphate deaminase 2 (GNPDA2), was associated with both BMI (P = 4 x 10(-4)) and asthma (P = .03). Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
CONCLUSIONS: SNPs within several genes showed associations to BMI and asthma at a genetic level, but none of these associations were significant after correction for multiple testing. Our analysis of known candidate genes reveals some evidence for shared genetics between asthma and obesity, but other shared genetic determinants are likely to be identified in novel loci.
J Allergy Clin Immunol. 2010 Sep;126(3):631-7.e1-8.
背景：流行病学研究一致显示，哮喘与肥胖存在着相关性，这可能与肥胖与哮喘存在共同性遗传特征有关。
目的：本文旨在研究与哮喘和肥胖相关的遗传变异。
方法：基于文献检索，从下列研究中寻找相关基因：(1)体重指数（BMI）相关基因组研究（GWASs）(n = 17 genes)；(2)哮喘的GWASs（n = 14）；(3)BMI和哮喘的候选基因研究（n = 7）。我们采用儿童哮喘管理项目的GWAS数据分析这些基因的单核苷酸多态性（SNPs）与哮喘（n=359）及BMI（n=537）之间的关系。
结果：一项有关BMI与GWAS SNP的研究显示，靠近氨基葡萄糖- 6 -磷酸脱氨酶（GNPDA2）的rs10938397与BMI（P = 4 x 10-4）和哮喘（P =0.03）相关。有关哮喘GWAS SNPs及候选基因SNPs的研究，并未发现BMI与哮喘的相关性。基于基因的分析包括了所有基因的SNPs，结果显示与某些基因的表型有关（P <0.05）。与BMI相关的基因包括：神经生长调节子（NEGR1）、环岛-轴突导向受体-同源物1（ROBO1）、甘油二酯激酶γ（DGKG）、Fas凋亡抑制分子（FAIM2）、脂肪量与肥胖相关基因（FTO）、碳水化合物（N-乙酰氨基4-0）磺基转移酶8（CHST8）；与哮喘相关基因包括：白介素1受体样1/白介素18受体1（IL1RL1/IL18R1）、二肽基肽酶10（DPP10）、磷酸二酯酶4D（PDE4D）、V-myb原粒细胞增多症病毒癌基因同源物（MYB）、PDE10A、IL33、D型蛋白酪氨酸磷酸酶受体（PTPRD）；哮喘和BMI候选基因包括：蛋白激酶Ca（PRKCA）。
结论：一些基因的SNPs显示在遗传水平上与BMI和哮喘都存在相关性，但经过多次测试校正后这些相关性并不显著。对已知的候选基因进行分析表明，有证据显示哮喘与肥胖之间存在遗传学相关性，但有必要寻找其他新的遗传决定因素。
（林江涛 审校）
J Allergy Clin Immunol. 2010 Sep;126(3):631-7.e1-8.
Analyses of shared genetic factors between asthma and obesity in children.
Melén E, Himes BE, Brehm JM, Boutaoui N, Klanderman BJ, Sylvia JS, Lasky-Su J.
Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass 02115, USA. erik.melen@ki.se
Abstract
BACKGROUND: Epidemiologic studies consistently show associations between asthma and obesity. Shared genetics might account for this association.
OBJECTIVE: We sought to identify genetic variants associated with both asthma and obesity.
METHODS: On the basis of a literature search, we identified genes from (1) genome-wide association studies (GWASs) of body mass index (BMI; n = 17 genes), (2) GWASs of asthma (n = 14), and (3) candidate gene studies of BMI and asthma (n = 7). We used GWAS data from the Childhood Asthma Management Program to analyze associations between single nucleotide polymorphisms (SNPs) in these genes and asthma (n = 359 subjects) and BMI (n = 537).
RESULTS: One top BMI GWAS SNP from the literature, rs10938397 near glucosamine-6-phosphate deaminase 2 (GNPDA2), was associated with both BMI (P = 4 x 10(-4)) and asthma (P = .03). Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
CONCLUSIONS: SNPs within several genes showed associations to BMI and asthma at a genetic level, but none of these associations were significant after correction for multiple testing. Our analysis of known candidate genes reveals some evidence for shared genetics between asthma and obesity, but other shared genetic determinants are likely to be identified in novel loci.
J Allergy Clin Immunol. 2010 Sep;126(3):631-7.e1-8.
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