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Cited by 72Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsDiabetes and associated disorders

Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes

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Guan, Fanglin, Niu, Yu, Zhang, Tianxiao, Liu, Songfang, Ma, Lei, Qi, Ting, Feng, Jia, Zuo, Hong +3 more·2016·Scientific Reports
DOI 10.1038/srep29586PMC PMC4944165
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Abstract

The SNP of rs964184 in ZPR1 has recently been associated with type 2 diabetes mellitus (T2DM) in Japanese individuals. To comprehensively investigate the association of common variants in ZPR1 with T2DM in Han Chinese individuals, we designed a two-stage case-control study of 3,505 T2DM patients and 6,911 unrelated healthy Han Chinese individuals. A total of 24 single nucleotide polymorphisms (SNPs) were genotyped and single-SNP association, imputation and gender-specific association analyses were performed. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 280. A novel SNP, rs2075290 and the previously reported SNP, rs964184, were significantly associated with T2DM in the two independent datasets and individuals harboring the CC genotype of rs2075290 and GG genotype of rs964184 exhibited higher levels of fasting plasma glucose (FPG) and blood hemoglobin A1c (HbA1c) than individuals of other genotypes. Additionally, haplotype analyses indicated that two haplotype blocks containing rs2075290 or rs964184 were also significantly associated with T2DM. In summary, these results suggest that ZPR1 plays an important role in the etiology of T2DM and this gene might be involved in abnormal glucose metabolism.

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  • ZPR1/ZNF259 promoter region has the binding sequence for PPARs, which may activate genes involved in glucose and cholesterol metabolism, including APOE, via hepatocyte nuclear factor 4 alpha activation.

    “ZPR1/ZNF259 promoter region has the binding sequence for PPARs, which may activate genes involved in glucose and cholesterol metabolism, including APOE, via hepatocyte nuclear factor 4 alpha activation [39].”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [39]

    The paper’s introductory passage (indexed under Abstract; no page number provided) says the ZPR1/ZNF259 promoter binds PPARG proteins 1 and 2, which bind HNF4α; it says HNF4α activates genes involved in glucose and cholesterol metabolism. It does not identify APOE as one of those genes. The Discussion mentions a different gene, APOA5, adjacent to ZPR1. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • rs964184 has been associated with triglycerides, type 2 diabetes, and abdominal aortic aneurysm.

    “has been associated with triglycerides [39, 40], type 2 diabetes [39] and abdominal aortic aneurysm (AAA) [41].”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [39]

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Authors
Guan, F., Niu, Y., Zhang, T., Liu, S., Ma, L., Qi, T., Feng, J., Zuo, H., Li, G., Liu, X., & Wang, S.
Affiliations
  • Xi'an Jiaotong University (CN)
  • Washington University in St. Louis (US)
Corresponding author
  • Niu, Yu
  • Wang, Shujin
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-07-14
Volume
6
Issue
1
Pages
29586-29586
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep29586
PMC
PMC4944165
OpenAlex
W2475363254
Cited by
72
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 18 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 16 · 2018: 15 · 2017: 9 · 2016: 2
FWCI
11.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (81401563)
  • Ministry of Education of the People's Republic of China (2013021120078)
  • China Postdoctoral Science Foundation (T70927)
  • Shaanxi Province Postdoctoral Science Foundation (201318420005)
  • Fundamental Research Funds for the Central Universities (08143003, 08142024)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
type 2 diabetes, ZPR1, single nucleotide polymorphisms, genetic susceptibility, Han Chinese, haplotype association, fasting blood glucose, HbA1c, glucose metabolism, genotype imputation
MeSH terms
Adult, Aged, Carrier Proteins, China, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Male, Middle Aged, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Membrane Transport Proteins, Asian People, Genetic Association Studies

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