GJB2
Connexins are involved in intracellular channels known as gap junctions that transport small molecules, including nutrients, ions and signalling molecules between cells. Connexin 26 is involved in gap junctions transporting calcium and potassium ions, as well as other small molecules. 1 Rare mutations affecting the amino-acid composition of the GJB2 protein are known to cause hearing loss due to its function in the ear. 2 However, GJB2 is also expressed in multiple other tissues and implicated in a plethora of other processes, including breathing, skin pathologies and cancer. 3 4 5 How exactly Connexin 26 affects lipid metabolism remains unclear, but other connexins have been implicated in the control of fat formation. 6
A20216312G
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) |
|---|---|---|---|
| rs112803755 | a | g | 3 |
Risk Description
Increased total triglyceride levels in the carriers of the risk allele that may be counteracted by fish oil supplementation.
A rare SNP linked with increased GJB2 expression levels in the fat tissue is also associated with the interaction effect of fish oil and triglyceride levels. 7 People carrying the rare G allele had on average higher triglyceride levels than those having the most common AA genotype. However, in the carriers of the G allele taking fish oil, triglyceride levels were actually lower than in the AA cohort. 7 The mechanisms of this effect, beyond the potential role of other connexins in the fat tissue 6, remain unclear.
The Gene x Environment genome-wide association study (GxE GWAS) for lipid levels with and without fish oil supplementation that detected this variant 7 was high-powered and used a replication cohort, followed by a joint meta-analysis of both cohorts. Therefore, these results deserve our attention. However, it must be noted that interpreting GxE interaction effects such as this one can be tricky, and the true phenomena behind them may sometimes be counterintuitive. 8 Therefore, acting on their results should be done with some caution.
Indirect Nutrients:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Fish Oil | Omega-3 Fatty Acids |
Fish oil may be particularly beneficial for people with the AG and GG genotypes at rs77542162 given the detected interaction effect of fish oil supplementation on triglyceride levels for this SNP. |
Discuss this information with your doctor before taking any course of action.
Citations:
- GJB2 gene review, Medline Plus, https://medlineplus.gov/genetics/gene/gjb2.
- Verselis VK. Connexin hemichannels and cochlear function. Neurosci Lett. 2019 Mar 16;695:40-45. doi: 10.1016/j.neulet.2017.09.020. Epub 2017 Sep 14. PMID: 28917982; PMCID: PMC5851822.
- van de Wiel J, Meigh L, Bhandare A, Cook J, Nijjar S, Huckstepp R, Dale N. Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata. Commun Biol. 2020 Sep 21;3(1):521. doi: 10.1038/s42003-020-01248-x.
- Iossa S, Marciano E, Franzé A. GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss. Curr Genomics. 2011 Nov;12(7):475-785. doi: 10.2174/138920211797904098. PMID: 22547955; PMCID: PMC3219843.
- Chen CX, Luo KJ, Yang JP, Huang YC, Cardenas ER, Nicholson BJ, Jiang JX. Connexins and cAMP Cross-Talk in Cancer Progression and Metastasis. Cancers (Basel). 2020 Dec 28;13(1):58. doi: 10.3390/cancers13010058.
- Zhu Y, Gao Y, Tao C, Shao M, Zhao S, Huang W, Yao T, Johnson JA, Liu T, Cypess AM, Gupta O, Holland WL, Gupta RK, Spray DC, Tanowitz HB, Cao L, Lynes MD, Tseng YH, Elmquist JK, Williams KW, Lin HV, Scherer PE. Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals. Cell Metab. 2016 Sep 13;24(3):420-433. doi: 10.1016/j.cmet.2016.08.005.
- Francis M, et al. Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci. PLoS Genet. 2021 Mar 24;17(3):e1009431. doi: 10.1371/journal.pgen.1009431.
- Thompson WD. Effect modification and the limits of biological inference from epidemiologic data. J Clin Epidemiol. 1991;44(3):221-32. doi: 10.1016/0895-4356(91)90033-6.