Interactions between the FTO and GNB3 Genes Contribute to Varied Clinical Phenotypes in Hypertension

Kumar, Rahul; Kohli, Samantha; Alam, Perwez; Barkotoky, Ritankur; Gupta, Mohit; Tyagi, Sanjay; Jain, Shivi; Pasha, M. A. Qadar

doi:10.1371/journal.pone.0063934

Cited by 15 publications

(4 citation statements)

References 49 publications

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“…Moreover, general linear models confirmed the interaction between FTO variant and hypertension. Similarly, many studies suggested that FTO variants contribute to higher blood pressure (Kumar et al, 2013;Pausova et al, 2009) and especially to obesity-related hypertension (He et al, 2014). The most convincing explanation for these findings is the interdependence of GGT and blood pressure, obesity, metabolic syndrome, and diabetes mellitus.…”

Section: Discussionmentioning

confidence: 96%

Association betweenFTO(rs17817449) genetic variant, gamma‐glutamyl transferase, and hypertension in Slovak midlife women

Falbová

Vorobeľová

Siváková

et al. 2021

American J Hum Biol

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Objectives: This cross-sectional study investigates associations between the FTO rs 17817449 genetic variant, liver enzymes, and hypertension in Slovak midlife women. Methods: We assessed 576 Slovak women aged 39 to 65 years. The women were interviewed and examined during their medical examination at local Health Centers and then divided into subgroups according to their blood pressure status; 255 women with hypertension and 321 normotensive. The FTO genetic variant was detected by polymerase chain reaction-restriction fragment length polymorphism. Resultant data was analyzed by linear regression analysis and general linear models to adjust for risk factors associated with gammaglutamyl transferase levels (GGT), including waist to hip ratio (WHR) and uric acid (UA). Results: A significant association between the FTO variant and GGT levels was observed in the hypertensive group after control for confounding covariates, including WHR and UA (p = .004). The predicted GGT level for GT/TT hypertensive carriers is 0.158 μkat/L higher than for GG carriers. Moreover, the two-way analysis of covariance revealed significant interaction between FTO effects and hypertension on logGGT levels (p = .042). Finally, hypertensive women with the T-allele had the highest estimated marginal mean value of logGGT at À0.39 μkat/L while the GG-genotype in both hypertensive and normotensive women had the lowest value at À0.54 μkat/L.Conclusions: This study suggests that the FTO (rs17817449) variant is associated with higher serum GGT levels in hypertensive midlife women.

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Section: Discussionmentioning

confidence: 96%

Association betweenFTO(rs17817449) genetic variant, gamma‐glutamyl transferase, and hypertension in Slovak midlife women

Falbová

Vorobeľová

Siváková

et al. 2021

American J Hum Biol

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“…Rod monochromats show a mosaic of pseudogenization with most of the phototransduction genes inactivated in multiple lineages, including SWS1, LWS, CNGB3, GNAT2, GNGT2, PDE6C and PDE6H. The pleiotropic GNB3 [46,47] is the only gene that has remained functional in all rod monochromats examined (figure 2).…”

Section: Resultsmentioning

confidence: 99%

Genomic evidence for rod monochromacy in sloths and armadillos suggests early subterranean history for Xenarthra

Emerling

Springer

2015

Proc. R. Soc. B.

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Rod monochromacy is a rare condition in vertebrates characterized by the absence of cone photoreceptor cells. The resulting phenotype is colourblindness and low acuity vision in dim-light and blindness in bright-light conditions. Early reports of xenarthrans (armadillos, sloths and anteaters) suggest that they are rod monochromats, but this has not been tested with genomic data. We searched the genomes of Dasypus novemcinctus (nine-banded armadillo), Choloepus hoffmanni (Hoffmann's two-toed sloth) and Mylodon darwinii (extinct ground sloth) for retinal photoreceptor genes and examined them for inactivating mutations. We performed PCR and Sanger sequencing on cone phototransduction genes of 10 additional xenarthrans to test for shared inactivating mutations and estimated the timing of inactivation for photoreceptor pseudogenes. We concluded that a stem xenarthran became an long-wavelength sensitive-cone monochromat following a missense mutation at a critical residue in SWS1, and a stem cingulate (armadillos, glyptodonts and pampatheres) and stem pilosan (sloths and anteaters) independently acquired rod monochromacy early in their evolutionary history following the inactivation of LWS and PDE6C, respectively. We hypothesize that rod monochromacy in armadillos and pilosans evolved as an adaptation to a subterranean habitat in the early history of Xenarthra. The presence of rod monochromacy has major implications for understanding xenarthran behavioural ecology and evolution.

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“…With the exception of CNGA3, all of the phototransduction genes with inactivating mutations in one or more cetacean rod monochromats also have inactivating mutations among non-cetacean rod monochromats including golden moles, sloths, and armadillos Springer, 2014, 2015). Among the phototransduction genes that we investigated, only GNB3 is intact in rod-monochromatic cetaceans, presumably because this gene is pleiotropic (Keers et al, 2011;Kumar et al, 2013).…”

Section: Inactivating Mutations In the Cetacean Cone Phototransductiomentioning

confidence: 99%

Inactivation of Cone-Specific Phototransduction Genes in Rod Monochromatic Cetaceans

et al. 2016

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Vertebrate vision is mediated by two types of photoreceptors, rod and cone cells. Rods are more sensitive than cones in dim light, but are incapable of color discrimination because they possess only one type of photosensitive opsin protein (rod opsin = RH1). By contrast, cones are more important for vision in bright light. Cones also facilitate dichromatic color vision in most mammals because there are two cone pigment genes (SWS1, LWS) that facilitate color discrimination. Cone monochromacy occurs when one of the cone opsins (usually SWS1) is inactivated and is present in assorted subterranean, nocturnal, and aquatic mammals. Rod monochromacy occurs when both cone photoreceptors are inactivated, resulting in a pure rod retina. The latter condition is extremely rare in mammals and has only been confirmed with genetic evidence in five cetacean lineages, golden moles, armadillos, and sloths. The first genetic evidence for rod monochromacy in these taxa consisted of inactivated copies of both of their cone pigment genes (SWS1, LWS). However, other components of the cone phototransduction cascade are also predicted to accumulate inactivating mutations in rod monochromats. Here, we employ genome sequences and exon capture data from four baleen whales (bowhead, two minke whales, fin whale) and five toothed whales (sperm whale, Yangtze River dolphin, beluga, killer whale, bottlenose dolphin) to test the hypothesis that rod monochromacy is associated with the inactivation of seven genes (GNAT2, GNB3, GNGT2, PDE6C, PDE6H, CNGA3, CNGB3) in the cone phototransduction cascade. Cone-monochromatic toothed whales that retain a functional copy of LWS (beluga whale, Yangtze River dolphin, killer whale, bottlenose dolphin) also retain intact copies of other cone-specific phototransduction genes, whereas rod monochromats (Antarctic minke whale, common minke whale, fin whale, bowhead whale, sperm whale) have inactivating mutations in five or more genes in the cone phototransduction cascade. The only shared inactivating mutations that were discovered occur in the three Balaenoptera species (two minke whales, fin whale), further suggesting that rod monochromacy evolved independently in two clades of baleen whales, Balaenopteroidea and Balaenidae. We estimate that rod monochromacy evolved first in Balaenopteroidea (∼28.8 Ma) followed by P. macrocephalus (∼19.5 Ma) and Balaenidae (∼13.0 Ma).

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Interactions between the FTO and GNB3 Genes Contribute to Varied Clinical Phenotypes in Hypertension

Cited by 15 publications

References 49 publications

Association betweenFTO(rs17817449) genetic variant, gamma‐glutamyl transferase, and hypertension in Slovak midlife women

Association betweenFTO(rs17817449) genetic variant, gamma‐glutamyl transferase, and hypertension in Slovak midlife women

Genomic evidence for rod monochromacy in sloths and armadillos suggests early subterranean history for Xenarthra

Inactivation of Cone-Specific Phototransduction Genes in Rod Monochromatic Cetaceans

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