HHEX基因的变异与日本人群患2型糖尿病的风险增加有关。
Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population.
作者信息
Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, Froguel P, Kadowaki T
机构信息
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
出版信息
Diabetologia. 2007 Dec;50(12):2461-6. doi: 10.1007/s00125-007-0827-5. Epub 2007 Oct 10.
AIMS/HYPOTHESIS: Recently, several groups have carried out whole-genome association studies in European and European-origin populations and found novel type 2 diabetes-susceptibility genes, fat mass and obesity associated (FTO), solute carrier family 30 (zinc transporter), member 8 (SLC30A8), haematopoietically expressed homeobox (HHEX), exostoses (multiple) 2 (EXT2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which had not been in the list of functional candidates. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) in these genes and type 2 diabetes in participants from the Japanese population.
METHODS
Sixteen previously reported SNPs were genotyped in 864 Japanese type 2 diabetes individuals (535 men and 329 women; age 63.1 +/- 9.5 years (mean+/-SD), BMI 24.3 +/- 3.9 kg/m(2)) and 864 Japanese control individuals (386 men and 478 women; age 69.5 +/- 6.8 years, BMI 23.8 +/- 3.7 kg/m(2)).
RESULTS
The SNPs rs5015480 [odds ratio (OR) = 1.46 (95% CI 1.20-1.77), p = 2.0 x 10(-4)], rs7923837 [OR = 1.40 (95% CI 1.17-1.68), p = 2.0 x 10(-4)] and rs1111875 [OR = 1.30 (95% CI 1.11-1.52), p = 0.0013] in HHEX were significantly associated with type 2 diabetes with the same direction as previously reported. SNP rs8050136 in FTO was nominally associated with type 2 diabetes [OR = 1.22 (95% CI 1.03-1.46), p = 0.025]. SNPs in other genes such as rs7756992 in CDKAL1, rs10811661 in CDKN2B and rs13266634 in SLC30A8 showed nominal association with type 2 diabetes. rs7756992 in CDKAL1 and rs10811661 in CDKN2B were correlated with impaired pancreatic beta cell function as estimated by the homeostasis model assessment beta index (p = 0.023, p = 0.0083, respectively).
CONCLUSIONS/INTERPRETATION: HHEX is a common type 2 diabetes-susceptibility gene across different ethnic groups.
目的/假设：最近，几个研究小组在欧洲及欧洲裔人群中开展了全基因组关联研究，发现了新的2型糖尿病易感基因，如脂肪量和肥胖相关基因（FTO）、溶质载体家族30（锌转运体）成员8（SLC30A8）、造血表达同源盒基因（HHEX）、多发外生骨疣2（EXT2）、CDK5调节亚基相关蛋白1样蛋白1（CDKAL1）、细胞周期蛋白依赖性激酶抑制剂2B（p15，抑制CDK4）（CDKN2B）以及胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2），这些基因并不在功能候选基因列表中。本研究的目的是确定这些基因中的单核苷酸多态性（SNP）与日本人群参与者的2型糖尿病之间的关联。
方法
对864例日本2型糖尿病患者（535例男性和329例女性；年龄63.1±9.5岁（均值±标准差），体重指数24.3±3.9kg/m²）和864例日本对照个体（386例男性和478例女性；年龄69.5±6.8岁，体重指数23.8±3.7kg/m²）的16个先前报道的SNP进行基因分型。
结果
HHEX基因中的SNP rs5015480 [优势比（OR）=1.46（95%可信区间1.20 - 1.77），p = 2.0×10⁻⁴]、rs7923837 [OR = 1.40（95%可信区间1.17 - 1.68），p = 2.0×10⁻⁴]和rs1111875 [OR = 1.30（95%可信区间1.11 - 1.52），p = 0.0013]与2型糖尿病显著相关，且方向与先前报道一致。FTO基因中的SNP rs8050136与2型糖尿病存在名义上的关联[OR = 1.22（95%可信区间1.03 - 1.46），p = 0.025]。其他基因中的SNP，如CDKAL1基因中的rs7756992、CDKN2B基因中的rs10811661和SLC30A8基因中的rs13266634与2型糖尿病存在名义上的关联。CDKAL1基因中的rs7756992和CDKN2B基因中的rs10811661与通过稳态模型评估β指数估计的胰岛β细胞功能受损相关（分别为p = 0.023，p = 0.0083）。
结论/解读：HHEX是不同种族中常见的2型糖尿病易感基因。
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