Noso Shinsuke, Ikegami Hiroshi, Fujisawa Tomomi, Kawabata Yumiko, Asano Katsuaki, Hiromine Yoshihisa, Tsurumaru Masako, Sugihara Shigetaka, Lee Inkyu, Kawasaki Eiji, Awata Takuya, Ogihara Toshio
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Diabetes. 2005 Dec;54(12):3582-6. doi: 10.2337/diabetes.54.12.3582.
Association studies are a potentially powerful approach to identifying susceptibility variants for common multifactorial diseases such as type 1 diabetes, but the results are not always consistently reproducible. The IDDM5 locus has recently been narrowed to an approximately 200-kb interval on chromosome 6q25 by two independent groups. These studies demonstrated that alleles at markers in the mitogen-activating protein kinase 7 interacting protein 2 (MAP3K7IP2)/SUMO4 region were associated with susceptibility to type 1 diabetes. Subsequent studies, however, showed inconsistency in the association of the SUMO4 gene with type 1 diabetes. To clarify the contribution of the M55V polymorphism of the SUMO4 gene to type 1 diabetes susceptibility, 541 type 1 diabetic patients and 768 control subjects were studied in Asian populations. The M55V polymorphism was significantly associated with type 1 diabetes in Asian populations (summary odds ratio [OR] 1.46, P = 0.00083, Mantel-Haenszel test). Meta-analysis of published studies and the present data confirmed a highly significant association in Asian populations (summary OR 1.29, P = 7.0 x 10(-6)) but indicated heterogeneity in the genetic effect of the SUMO4/MAP3K7IP2 locus on type 1 diabetes among diverse ethnic groups. These data indicate that the MAP3K7IP2/SUMO4 locus in the IDDM5 interval is associated with type 1 diabetes in Asian populations.
关联研究是识别常见多因素疾病（如1型糖尿病）易感性变异的一种潜在有力方法，但结果并非总是能一致地重复验证。最近，两个独立研究小组已将IDDM5基因座定位到6号染色体6q25上一个约200 kb的区间。这些研究表明，丝裂原活化蛋白激酶7相互作用蛋白2（MAP3K7IP2）/SUMO4区域内标记物的等位基因与1型糖尿病易感性相关。然而，后续研究显示SUMO4基因与1型糖尿病的关联并不一致。为了阐明SUMO4基因M55V多态性对1型糖尿病易感性的作用，对亚洲人群中的541例1型糖尿病患者和768例对照者进行了研究。在亚洲人群中，M55V多态性与1型糖尿病显著相关（综合优势比[OR]为1.46，P = 0.00083，Mantel-Haenszel检验）。对已发表研究和本研究数据的荟萃分析证实，在亚洲人群中存在高度显著的关联（综合OR为1.29，P = 7.0×10⁻⁶），但表明SUMO4/MAP3K7IP2基因座对不同种族1型糖尿病的遗传效应存在异质性。这些数据表明，IDDM5区间内的MAP3K7IP2/SUMO4基因座与亚洲人群的1型糖尿病相关。
