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Diabetes. 2018 May;67(5):861-871. doi: 10.2337/db17-0852. Epub 2018 Feb 26.

HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Author information

1
The Center of Immunological Genetics and HLA Typing, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China shenjie@njmu.edu.cn tingwei.guo@einstein.yu.edu tingweiguo@gmail.com.
2
Department of Endocrinology and Metabolism, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
3
Department of Internal Medicine, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China shenjie@njmu.edu.cn tingwei.guo@einstein.yu.edu tingweiguo@gmail.com.
4
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY.
5
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
6
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.
7
The Center of Immunological Genetics and HLA Typing, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
8
Flow Cytometry Core Facility, Albert Einstein College of Medicine, Bronx, NY.
9
HLA Laboratory, Beijing Red Cross Blood Center, Beijing, China.
10
The Key Laboratory of Geriatrics, Beijing Hospital, and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
11
Quality Control Laboratory, China Bone Marrow Program, Beijing, China.
12
HLA Laboratory, Chongqing Blood Center, Chongqing, China.
13
HLA Laboratory, Zhejiang Blood Center, Hangzhou, Zhejiang, China.
14
HLA Laboratory, Liaoning Blood Center, Shenyang, Liaoning, China.
15
HLA Laboratory, Hebei Blood Center, Shijiazhuang, Hebei, China.
16
HLA Laboratory, Taiyuan Red Cross Blood Center, Taiyuan, Shanxi, China.
17
HLA Laboratory, Shaanxi Blood Center, Xi'an, Shaanxi, China.
18
HLA Laboratory, Henan Blood Center, Zhengzhou, Henan, China.
19
HLA Laboratory, Shandong Blood Center, Jinan, Shandong, China.
20
The Key Laboratory of Histocompatibility and Immunogenetics, Shenzhen Blood Center, Shenzhen, Guangdong, China.
21
HLA Laboratory, Dalian Red Cross Blood Center, Dalian, Liaoning, China.
22
HLA Laboratory, Institute of Blood Transfusion, Chinese Academy of Medical Sciences, and Peking Union Medical College, Chengdu, Sichuan, China.
23
HLA Laboratory, Jiangxi Blood Center, Nanchang, Jiangxi, China.
24
Department of Health Education, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
25
HLA Laboratory, Xinjiang Blood Center, Urumchi, Xinjiang, China.
26
HLA Laboratory, Kunming Blood Center, Kunming, Yunnan, China.
27
HLA Laboratory, Hefei Red Cross Blood Center, Hefei, Anhui, China.
28
HLA Laboratory, Gansu Red Cross Blood Center, Lanzhou, Gansu, China.
29
HLA Laboratory, Nanning Blood Center, Nanning, Guangxi, China.
30
HLA Laboratory, Xiamen Blood Center, Xiamen, Fujian, China.
31
HLA Laboratory, Changchun Blood Center, Changchun, Jilin, China.
32
HLA Laboratory, Wuhan Blood Center, Wuhan, Hubei, China.
33
HLA Laboratory, Harbin Red Cross Blood Center, Harbin, Heilongjiang, China.
34
HLA Laboratory, Qingdao Blood Center, Qingdao, Shandong, China.
35
HLA Laboratory, Yueyang Red Cross Blood Center, Yueyang, Hunan, China.
36
HLA Laboratory, Changsha Blood Center, Changsha, Hunan, China.
37
HLA Laboratory, Soochow Red Cross Blood Center, Suzhou, Jiangsu, China.
38
Department of Endocrinology, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
39
HLA Laboratory, CapitalBio Corporation, Beijing, China.
40
HLA Laboratory, Beijing Genomics Institute, Shenzhen, Guangdong, China.
41
Department of HLA Technology, China Bone Marrow Program, Beijing, China.
42
Department of Urology, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
43
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Abstract

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.

PMID:
29483183
PMCID:
PMC6463754
DOI:
10.2337/db17-0852
[Indexed for MEDLINE]
Free PMC Article

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