Genetic modifiers of cystic fibrosis-related diabetes.
Genetic modifiers of cystic fibrosis-related diabetes.
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DOI：
10.2337/db13-0510
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发表时间：
2013-10
期刊：
影响因子：
7.7
通讯作者：
Cutting GR
中科院分区：
文献类型：
--
作者：
Blackman SM;Commander CW;Watson C;Arcara KM;Strug LJ;Stonebraker JR;Wright FA;Rommens JM;Sun L;Pace RG;Norris SA;Durie PR;Drumm ML;Knowles MR;Cutting GR
糖尿病是一种常见的年龄依赖性囊性纤维化（CF）并发症，受修饰基因的强烈影响。我们对3059例CF患者（644例CF相关性糖尿病[CFRD]）进行了全基因组关联研究，发现SLC26A9基因和5′内的单核苷酸多态性（snp）与CFRD相关（风险比[HR] 1.38; P = 3.6 × 10−8）。694例个体（124例CFRD）出现重复（HR, 1.47; P = 0.007），联合分析P = 9.8 × 10−10显著。SLC26A9是一个上皮氯/碳酸氢盐通道，可以与CF跨膜调节因子（CFTR）相互作用，CFTR是CF中突变的蛋白。我们还假设与2型糖尿病相关的常见snp也可能影响CFRD的风险。本研究重复了先前CFRD与TCF7L2 snp的关联（P = 0.004；联合分析P = 3.8 × 10−6），CDKAL1、CDKN2A/B和IGF2BP2位点或附近的2型糖尿病snp与CFRD相关（P < 0.004）。这5个基因座占CFRD发病表型变异的8.3%，总人群归因风险为68%。糖尿病是CF的一种非常普遍的并发症，其易感性部分由SLC26A9（介导CF致病基因附近的过程）和普通人群中4个2型糖尿病易感性位点的变异决定。
Diabetes is a common age-dependent complication of cystic fibrosis (CF) that is strongly influenced by modifier genes. We conducted a genome-wide association study in 3,059 individuals with CF (644 with CF-related diabetes [CFRD]) and identified single nucleotide polymorphisms (SNPs) within and 5′ to the SLC26A9 gene that associated with CFRD (hazard ratio [HR] 1.38; P = 3.6 × 10−8). Replication was demonstrated in 694 individuals (124 with CFRD) (HR, 1.47; P = 0.007), with combined analysis significant at P = 9.8 × 10−10. SLC26A9 is an epithelial chloride/bicarbonate channel that can interact with the CF transmembrane regulator (CFTR), the protein mutated in CF. We also hypothesized that common SNPs associated with type 2 diabetes also might affect risk for CFRD. A previous association of CFRD with SNPs in TCF7L2 was replicated in this study (P = 0.004; combined analysis P = 3.8 × 10−6), and type 2 diabetes SNPs at or near CDKAL1, CDKN2A/B, and IGF2BP2 were associated with CFRD (P < 0.004). These five loci accounted for 8.3% of the phenotypic variance in CFRD onset and had a combined population-attributable risk of 68%. Diabetes is a highly prevalent complication of CF, for which susceptibility is determined in part by variants at SLC26A9 (which mediates processes proximate to the CF disease-causing gene) and at four susceptibility loci for type 2 diabetes in the general population.
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DOI：
10.1085/jgp.200810097
发表时间：
2009-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bertrand CA;Zhang R;Pilewski JM;Frizzell RA
通讯作者：
Frizzell RA
DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
人类胰岛中的开放染色质图。
影响因子：
30.8
作者：
Gaulton, Kyle J.;Nammo, Takao;Pasquali, Lorenzo;Simon, Jeremy M.;Giresi, Paul G.;Fogarty, Marie P.;Panhuis, Tami M.;Mieczkowski, Piotr;Secchi, Antonio;Bosco, Domenico;Berney, Thierry;Montanya, Eduard;Mohlke, Karen L.;Lieb, Jason D.;Ferrer, Jorge
通讯作者：
Ferrer, Jorge
影响因子：
3.7
作者：
Guo N;Parry EM;Li LS;Kembou F;Lauder N;Hussain MA;Berggren PO;Armanios M
通讯作者：
Armanios M