Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans.
Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans.
复制标题
GLIS3 和 CRY2 的变异与中国汉族人的 2 型糖尿病和空腹血糖受损有关。
DOI：
10.1371/journal.pone.0021464
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Liu C;Li H;Qi L;Loos RJ;Qi Q;Lu L;Gan W;Lin X
最近的全基因组关联研究已经确定了一些常见的变异与空腹血糖稳态和2型糖尿病的欧洲血统的人口。本研究是一项重复性研究，旨在探讨这种关联是否也存在于中国汉族人群中。我们对来自北京和上海的3，210名无关中国汉族人进行了MADD、ADRA 2A、ADRA 2、GLIS 3、PROX 1、FADS 1、C2 CD 4 B、IGF 1和IRS 1的9种变异或其附近的基因分型。我们证实了GLIS 3-rs7034200与空腹血糖（β = 0.07 mmol/l，P = 0.03）、β细胞功能（HOMA-B）（β = − 3.03%，P = 0.009）和2型糖尿病（OR [95%CI]= 1.27 [1.09-1.49]，P = 0.003）的相关性，调整了年龄、性别、地区和BMI。 在调整了其他糖尿病相关危险因素（包括糖尿病家族史、血脂谱、药物信息、高血压和生活方式因素）后，2型糖尿病的相关性仍然显著，而进一步调整HOMA-B则消除了相关性。A等位基因rs 11605924与IFG/2型糖尿病合并风险增加中度相关（OR [95%CI]= 1.15[1.01-1.30]，P = 0.04）。 MADD、ADRA 2A、PROX 1、FADS 1、C2 CD 4 B、IGF 1和IRS 1中或附近的SNP与2型糖尿病或相关血糖性状无显著相关性（P≥ 0. 10）。总之，我们的研究结果表明，GLIS 3基因座与中国汉族人2型糖尿病和空腹血糖受损，部分介导的β细胞功能受损。此外，我们还发现了IFG/2型糖尿病合并IFG/rs 11605924相关的适度证据。
Recent genome-wide association studies have identified a number of common variants associated with fasting glucose homeostasis and type 2 diabetes in populations of European origin. This is a replication study to examine whether such associations are also observed in Chinese Hans. We genotyped nine variants in or near MADD, ADRA2A, CRY2, GLIS3, PROX1, FADS1, C2CD4B, IGF1 and IRS1 in a population-based cohort including 3,210 unrelated Chinese Hans from Beijing and Shanghai. We confirmed the associations of GLIS3-rs7034200 with fasting glucose (beta = 0.07 mmol/l, P = 0.03), beta cell function (HOMA-B) (beta = −3.03%, P = 0.009), and type 2 diabetes (OR [95%CI] = 1.27 [1.09–1.49], P = 0.003) after adjustment for age, sex, region and BMI. The association for type 2 diabetes remained significant after adjusting for other diabetes related risk factors including family history of diabetes, lipid profile, medication information, hypertension and life style factors, while further adjustment for HOMA-B abolished the association. The A-allele of CRY2-rs11605924 was moderately associated with increased risk of combined IFG/type 2 diabetes (OR [95%CI] = 1.15[1.01–1.30], P = 0.04). SNPs in or near MADD, ADRA2A, PROX1, FADS1, C2CD4B, IGF1, and IRS1 did not exhibit significant associations with type 2 diabetes or related glycemic traits (P≥0.10). In conclusion, our results indicate the associations of GLIS3 locus with type 2 diabetes and impaired fasting glucose in Chinese Hans, partially mediated through impaired beta-cell function. In addition, we also found modest evidence for the association of CRY2-rs11605924 with combined IFG/type 2 diabetes.