Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Hjort, Rebecka ; Löfvenborg, Josefin E. ; Ahlqvist, Emma LU ; Alfredsson, Lars ; Andersson, Tomas ; Grill, Valdemar ; Groop, Leif LU ; Sørgjerd, Elin P. ; Tuomi, Tiinamaija LU orcid and Åsvold, Bjørn Olav , et al. (2019) In The Journal of clinical endocrinology and metabolism 104(10). p.4815-4826
Abstract

OBJECTIVE: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. METHODS: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical... (More)

OBJECTIVE: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. METHODS: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). RESULTS: The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. CONCLUSIONS: Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANDIS, diabetes, diabetics
in
The Journal of clinical endocrinology and metabolism
volume
104
issue
10
pages
12 pages
publisher
Oxford University Press
external identifiers
  • pmid:31125083
  • scopus:85071997740
ISSN
1945-7197
DOI
10.1210/jc.2019-00183
language
English
LU publication?
yes
id
c8308e5a-1405-4c99-9c93-c68e2e5d5b4c
date added to LUP
2019-09-16 13:18:50
date last changed
2024-03-19 20:26:18
@article{c8308e5a-1405-4c99-9c93-c68e2e5d5b4c,
  abstract     = {{<p>OBJECTIVE: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. METHODS: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). RESULTS: The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. CONCLUSIONS: Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.</p>}},
  author       = {{Hjort, Rebecka and Löfvenborg, Josefin E. and Ahlqvist, Emma and Alfredsson, Lars and Andersson, Tomas and Grill, Valdemar and Groop, Leif and Sørgjerd, Elin P. and Tuomi, Tiinamaija and Åsvold, Bjørn Olav and Carlsson, Sofia}},
  issn         = {{1945-7197}},
  keywords     = {{ANDIS; diabetes; diabetics}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{4815--4826}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of clinical endocrinology and metabolism}},
  title        = {{Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes}},
  url          = {{http://dx.doi.org/10.1210/jc.2019-00183}},
  doi          = {{10.1210/jc.2019-00183}},
  volume       = {{104}},
  year         = {{2019}},
}