Evidence map›Paper›PMID 32025861›Full record

ArticleActa diabetologica2020

A rare missense variant in the milk fat globule-EGF factor 8 (MFGE8) increases T2DM susceptibility and cardiovascular disease risk with population-specific effects.

Bishwa R Sapkota, Dharambir K Sanghera

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta diabetologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
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  5. Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Bishwa R SapkotaDepartment of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Rm 317 BMSB, Oklahoma City, OK, 73104, USA.
Dharambir K SangheraDepartment of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Rm 317 BMSB, Oklahoma City, OK, 73104, USA. Dharambir-sanghera@ouhsc.edu.ORCID http://orcid.org/0000-0001-7203-8655
University of Oklahoma Health Sciences Center · US

Funding

Genome, Metabolome, Ancestry and Diabetes Health DisparityR01DK118427 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI DUGGIRALA, RAVINDRANATH, GORING, HARALD HEINZ HERBERT · 2019 to 2023
$2.5M
Genome-wide Association Scan to Identify Risk Genes for Type 2 Diabetes in AsianR01DK082766 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SANGHERA, DHARAMBIR K. · 2009 to 2011
$2.3M
NIDDK NIH HHS R01 DK082766NIDDK NIH HHS R01DK082766NIDDK NIH HHS R01 DK118427
6 · The paper itself

Abstract

aimsThe milk fat globule-epidermal growth factor 8 (MFGE8), also called lactadherin, is an integrin ligand and a known mediator of inflammation and atherosclerosis in T2DM in studies using animal models. However, its role in the pathophysiology of human T2DM, obesity, and cardiovascular disease has been poorly explored. Aim of this study  was to investigate the role of a missense variant (rs371227978 C/T: Arg148His) in the MFGE8 gene identified through exome sequencing for its association with T2DM and cardiometabolic traits.

methodsExome-wide sequencing was performed using DNA samples from 68 Sikh individuals from multi-generation pedigrees affected with diabetes on Illumina's GAIIx using "SureSelect Human All Exon" panels. We further replicated this variant by de novo genotyping in a total of 4242 individuals of the Asian Indian Diabetic Heart Study/Sikh Diabetes Study using custom TaqMan genotyping assay. We also measured circulating concentrations of Mfge8 using frozen serum aliquots by enzyme-linked immunosorbent assay.

resultsOverall, only 1.78% of 4242 individuals were carriers of this variant with MAF being 0.009. Except for the significant correlation of this variant with T2DM and triglycerides, no other quantitative risk phenotype was significant. The minor per allele-associated increased risk for T2DM showed odds ratio of 1.95 (95% CI 1.18-3.23; p = 0.008) in unadjusted model and was 1.73 (95% CI 1.02-2.93; p = 0.043) after adjusting for the age, gender, and BMI. However, there was a strong correlation between serum Mfge8 concentrations with T2DM, (r

conclusionsHere, we report for the first time a novel population-specific rare variant in the MFGE8 gene linked with the increased Mfge8 concentrations and the risk for developing T2DM and cardiovascular risk factors in a population of Punjabi Sikhs from India. In view of a strong evidence from animal studies supporting the role of Mfge8 in obesity, insulin resistance, and the development of atherosclerosis in T2DM, our findings are important and timely. If validated in a large independent dataset, early screening of Mfge8 in blood levels may especially benefit those patients with genetically elevated Mfge8 levels to preventing or reducing the risk of T2DM and cardiovascular disease.

Indexed as

AdultAgedAged, 80 and overAnimalsAntigens, SurfaceAsian PeopleCardiovascular DiseasesCase-Control StudiesDiabetes Mellitus, Type 2Diabetic AngiopathiesEthnicityExome SequencingFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseAntigens, SurfaceMFGE8 protein, humanMilk ProteinsExome sequencingHypertriglyceridemiaMFGE8Population-specific rare variantPunjabi SikhsType 2 diabetes mellitus

Identifiers

PMID32025861
PMCPMC10502938
OpenAlexW3004698541

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.