• B Acad Nat Med Paris · Dec 2021

    Diabetes, cigarette smoking and transcription factor 7-like 2 (Tcf7L2) in the UK Biobank cohort.

    • S Lehrer and P H Rheinstein.
    • Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, United States.
    • B Acad Nat Med Paris. 2021 Dec 1; 205 (9): 114611501146-1150.

    Background —Smokers are 30 to 40 percent more likely to develop type 2 diabetes than non-smokers. A type 2 diabetes gene, Tcf7L2, which had lost activity, caused rats to consume more nicotine. In the present study, we used data from the UK Biobank to examine the relationship of smoking, type 2 diabetes, and Tcf7L2 in human subjects.Methods —The Tcf7L2 gene has two SNPs, rs7903146 and rs4506565, reported to be associated with type 2 diabetes. They have approximately equal power to estimate risk for type 2 diabetes, and the results from one correlate 92% with the other. We examined the genotypes of these SNPs and cigarette consumption.Results —Genotype TT, linked to type 2 diabetes, smoked the least. But because of the large sample size (approximately 111,000 subjects) the tiny difference in cigarettes smoked daily by each genotype group (effect size), while statistically significant, is probably clinically meaningless. The average subject smoked 19 cigarettes daily, with a difference of 0.12 cigarette between each genotype group.Conclusion —The fact that Tcf7L2 is involved in nicotine addiction in rats but not in humans, as UKBB data suggest, is hardly surprising. Humans and rodents descended from a common ancestor about 80 million years ago, with rats and mice diverging between 12 and 24 million years ago. Thus, over millions of years Tcf7L2 may have developed vastly different functions in rodents and humans. Genome Wide Association Studies have revealed at least 65 different loci linked to type 2 diabetes. Genes associated with type 2 diabetes include Tcf7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, IGF2BP2, SLC30A8, JAZF1, HHEX, DGKB, CDKN2A, CDKN2B, KCNQ1, HNF1A, HNF1B MC4R, GIPR, HNF4A, MTNR1B, PARG6, ZBED3, SLC30A8, CDKAL1, GLIS3, GCK, GCKR, among others. Perhaps one or more of these genes might be the intermediary between type 2 diabetes and cigarette smoking. Further studies are warranted.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…