Genome-Wide Association Study Confirming a Strong Effect of HLA and Identifying Variants in CSAD/Inc-ITGB7-1 on Chromosome 12q13.13 Associated With Susceptibility to Fulminant Type 1 Diabetes

被引：30

作者：

Kawabata, Yumiko ^{[1
]}

Nishida, Nao ^{[2
,3
]}

Awata, Takuya ^{[4
]}

Kawasaki, Eiji ^{[5
]}

Imagawa, Akihisa ^{[6
]}

Shimada, Akira ^{[7
]}

Osawa, Haruhiko ^{[8
]}

Tanaka, Shoichiro ^{[9
]}

Takahashi, Kazuma ^{[10
,11
]}

Nagata, Masao ^{[12
]}

Yasuda, Hisafumi ^{[13
]}

Uchigata, Yasuko ^{[14
]}

Kajio, Hiroshi ^{[15
]}

Makino, Hideichi ^{[16
]}

Yasuda, Kazuki ^{[17
]}

Kobayashi, Tetsuro ^{[18
]}

Hanafusa, Toshiaki ^{[19
]}

Tokunaga, Katsushi ^{[3
]}

Ikegami, Hiroshi ^{[1
]}

机构：

[1] Kindai Univ, Dept Endocrinol Metab & Diabet, Fac Med, Osaka, Japan

[2] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Chiba, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, Japan

[4] Int Univ Hlth & Welf Hosp, Dept Diabet Metab & Endocrinol, Yaita, Tochigi, Japan

[5] Shin Koga Hosp, Ctr Diabet, Fukuoka, Fukuoka, Japan

[6] Osaka Med Coll, Dept Internal Med 1, Osaka, Japan

[7] Saitama Med Univ, Dept Endocrinol & Diabet, Saitama, Japan

[8] Ehime Univ, Sch Med, Dept Lab Med, Matsuyama, Ehime, Japan

[9] Ai Home Clin Toshima, Tokyo, Japan

[10] Iwate Prefectural Univ, Fac Nursing, Takizawa, Iwate, Japan

[11] Iwate Prefectural Univ, Grad Sch Nursing, Takizawa, Iwate, Japan

[12] Takasago Municipal Hosp, Dept Internal Med, Takasago, Hyogo, Japan

[13] Kobe Univ, Grad Sch Hlth Sci, Dept Publ Hlth, Div Hlth Sci, Kobe, Hyogo, Japan

[14] Tokyo Womens Med Univ, Sch Med, Ctr Diabet, Tokyo, Japan

[15] Natl Ctr Global Hlth & Med, Ctr Hosp, Dept Diabet Endocrinol & Metab, Tokyo, Japan

[16] Shiraishi Hosp, Ctr Diabet, Imabari, Ehime, Japan

[17] Natl Ctr Global Hlth & Med, Res Inst, Diabet Res Ctr, Dept Metab Disorder, Tokyo, Japan

[18] Okinaka Mem Inst Med Res, Tokyo, Japan

[19] Sakai City Med Ctr, Sakai, Osaka, Japan

来源：

DIABETES | 2019年 / 68卷 / 03期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

GENETIC-VARIATION; DIAGNOSTIC-CRITERIA; MELLITUS; TAURINE; ONSET; CELL; EXPRESSION; COMMITTEE; INSULITIS; INTEGRIN;

D O I：

10.2337/db18-0314

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The first genome-wide association study of fulminant type 1 diabetes was performed in Japanese individuals. As previously reported using a candidate gene approach, a strong association was observed with multiple single nucleotide polymorphisms (SNPs) in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region (P = 1.56 x 10(-23), odds ratio [OR] 3.18). In addition, rs11170445 in CSAD/Inc-ITGB7-1 on chromosome 12q13.13 showed an association at a genome-wide significance level (P = 7.58 x 10(-9), OR 1.96). Fine mapping of the region revealed that rs3782151 in CSAD/Inc-ITGB7-1 showed the lowest P value (P = 4.60 x 10(-9), OR 1.97 [95% CI 1.57-2.48]). The risk allele of rs3782151 is a cis expression quantitative trait locus for ITGB7 that significantly increases the expression of this gene. CSAD/Inc-ITGB7-1 was found to be strongly associated with susceptibility to fulminant, but not classical, auto immune type 1 diabetes, implicating this locus in the distinct phenotype of fulminant type 1 diabetes.

引用

页码：665 / 675

页数：11

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