Association Between Liver-Specific Gene Polymorphisms and Their Expression Levels With Nonalcoholic Fatty Liver Disease

Adams, Leon A.; White, Scott W.; Marsh, Julie A.; Lye, Stephen J.; Connor, Kristin L.; Maganga, Richard; Ayonrinde, Oyekoya T.; Olynyk, John K.; Mori, Trevor A.; Beilin, Lawrence J.; Palmer, Lyle J.; Hamdorf, Jeffrey M.; Pennell, Craig E.

doi:10.1002/hep.26184

Cited by 71 publications

(74 citation statements)

References 39 publications

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“…For control of NAFLD, the role of other players within the vitamin D pathway is worthy of further consideration. For example, circulating levels of the vitamin D binding protein GC inversely correlate with liver steatosis, and may determine the ability of vitamin D to modulate the development of NAFLD (37). In addition, 1,25(OH) 2 D may act through the vitamin D receptor to improve insulin sensitivity (38).…”

Section: Discussionmentioning

confidence: 99%

Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

et al. 2014

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The role of vitamin D in curtailing the development of obesity and comorbidities such as the metabolic syndrome (MetS) and type 2 diabetes has received much attention recently. However, clinical trials have failed to conclusively demonstrate the benefits of vitamin D supplementation. In most studies, serum 25-hydroxyvitamin D [25(OH)D] decreases with increasing BMI above normal weight. These low 25(OH)D levels may also be a proxy for reduced exposure to sunlight-derived ultraviolet radiation (UVR). Here we investigate whether UVR and/or vitamin D supplementation modifies the development of obesity and type 2 diabetes in a murine model of obesity. Long-term suberythemal and erythemal UVR significantly suppressed weight gain, glucose intolerance, insulin resistance, nonalcoholic fatty liver disease measures; and serum levels of fasting insulin, glucose, and cholesterol in C57BL/6 male mice fed a high-fat diet. However, many of the benefits of UVR were not reproduced by vitamin D supplementation. In further mechanistic studies, skin induction of the UVR-induced mediator nitric oxide (NO) reproduced many of the effects of UVR. These studies suggest that UVR (sunlight exposure) may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D but dependent on other UVR-induced mediators such as NO.Obesity has significant effects on our health and wellbeing: obese people have increased comorbidities resulting from cardiovascular disease, type 2 diabetes, breast and colon cancers, dementia, and depression. Vitamin D deficiency is recognized as a health problem affecting many individuals worldwide (1) and may contribute to the development of obesity. Insufficient levels of vitamin D are associated with obesity, and obese people are more likely than others to be vitamin D deficient (reviewed in Earthman et al.

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Section: Discussionmentioning

confidence: 99%

Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

et al. 2014

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“…Although we did not have a healthy comparison population, reports of average VDBP levels in healthy children range from 232 to 298 mg/ml in pediatric populations of European ancestry using the same assay (52,53). A mean of 197 mg/ml was reported in young healthy children, 65% Hispanic and 23.4% African American, using a different assay (immunonephelometry) (39), whereas mean levels of 330 to 437 mg/ml have been reported in healthy children using radial immunodiffusion (54,55).…”

Section: Discussionmentioning

confidence: 99%

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) ,20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acutephase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. Methods:We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. Measurements and Main Results:We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 mg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age ,1 year, nonwhite race, being previously healthy, 25(OH)D ,20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P , 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = 20.24, P , 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

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“…This data indicate the existence of an important genetic basis for this disorder in that population. In order to discover single nucleotide polymorphisms (SNPs) associated with NAFLD, several genome-wide association studies (GWAS) have been carried out in HIV-uninfected individuals of several ethnicities [6][7][8][9][10][11]. These studies have identified several SNPs independently associated with NAFLD located within or close to different loci including PNPLA3, COL13A1, EFAB4B, EHBP1L1, FDFT1, GCKR, LYPLAL1, NCAN, PPP1R3B, GC, LCP1, LPPR4, SLC38A8, PARVB, and SAMM50 genes.…”

Section: Introductionmentioning

confidence: 99%

Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals

Macı́as

Rivero‐Juárez

Neukam

et al. 2015

Aids

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Association Between Liver-Specific Gene Polymorphisms and Their Expression Levels With Nonalcoholic Fatty Liver Disease

Cited by 71 publications

References 39 publications

Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

Ultraviolet Radiation Suppresses Obesity and Symptoms of Metabolic Syndrome Independently of Vitamin D in Mice Fed a High-Fat Diet

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals

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