Koo Bo Kyung, Cho Young Min, Kimm Kuchan, Lee Jong-Young, Oh Bermseok, Park Byung Lae, Cheong Hyun Sub, Shin Hyoung Doo, Ko Kyung Soo, Park Sang Gyu, Lee Hong Kyu, Park Kyong Soo
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Korean Diabetes J. 2010 Aug;34(4):229-36. doi: 10.4093/kdj.2010.34.4.229. Epub 2010 Aug 31.
The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.
We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.
No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).
Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.
据报道,Reg基因在再生胰岛中表达,且Reg1蛋白在小鼠糖尿病早期上调。由于人类Reg1α与小鼠Reg1同源,我们研究了Reg1α中的常见变异是否与韩国人群的2型糖尿病相关。
我们对24份韩国人DNA样本的Reg1α基因进行测序,以鉴定常见多态性。在发现的11种多态性中,对752例2型糖尿病患者和642例非糖尿病受试者进行了5种常见多态性(g.-385T>C [rs10165462]、g.-36T>G [rs25689789]、g.209G>T [rs2070707]、g.1385C>G [新发现]和g.2199G>A [新发现])的基因分型。
没有多态性与2型糖尿病风险相关。然而,g.-385C和g.2199A降低了早发型2型糖尿病的风险,早发型2型糖尿病定义为诊断时年龄在25岁及以上但小于40岁的受试者(g.-385C和g.2199A的比值比[OR]分别为0.721 [0.535至0.971]和0.731 [0.546至0.977]),而g.1385G增加了早发型糖尿病的风险(OR,1.398 [1.055至1.854])。尽管对多重假设检验中的误差进行校正后显示这三种个体多态性与早发型糖尿病之间无统计学显著关联,但由g.-385C、g.1385C和g.2199A组成的单倍型H1与早发型糖尿病风险降低相关(OR,0.590 [0.396至0.877],P = 0.009)。
虽然Reg1α中的多态性未被发现与2型糖尿病的总体易感性相关,但在韩国人群中,一些多态性与早发型2型糖尿病存在适度关联。