Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study

Legry, Vanessa; Goumidi, Louisa; Huyvaert, Marlène; Cottel, Dominique; Ferrières, Jean; Arveiler, Dominique; Bingham, Annie; Wagner, Anne; Ruidavets, Jean‐Bernard; Ducimetière, Pierre; Amouyel, Philippe; Meirhaeghe, Aline

doi:10.1016/j.diabet.2008.12.005

Cited by 15 publications

(13 citation statements)

References 19 publications

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“…Furthermore, the G allele of rs6511435 tended to be associated with a 20% higher risk of metabolic syndrome and obese patients carrying such allele had significantly higher plasma insulin levels than AA subjects ( P = 0.0055). Instead, no significant association was detected for rs11671983 and rs15723 (74). …”

Section: Angptl6mentioning

confidence: 83%

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Angiopoietin-Like Proteins: A Comprehensive Look

2014

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Angiopoietin-like proteins (ANGPTLs) are a family of proteins structurally similar to the angiopoietins. To date, eight ANGPTLs have been discovered, namely ANGPTL1 to ANGPTL8. Emerging evidence implies a key role for ANGPTLs in the regulation of a plethora of physiological and pathophysiological processes. Most of the ANGPTLs exhibit multibiological properties, including established functional roles in lipid and glucose metabolism, inflammation, hematopoiesis, and cancer. This report represents a systematic and updated appraisal of this class of proteins, focusing on the main features of each ANGPTL.

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Section: Angptl6mentioning

confidence: 83%

“…In another study, four single nucleotide polymorphisms (SNPs: rs6511435, rs8112063, rs11671983, and rs15723) were found to cover more than 95% of the known ANGPTL6 genetic variability. Subjects from the entire “MONICA-Study” were genotyped for these SNPs (74). The G allele of rs8112063 was associated with lower plasma glucose levels.…”

Section: Angptl6mentioning

confidence: 99%

Angiopoietin-Like Proteins: A Comprehensive Look

2014

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“…It would be of interest to investigate whether ANGPTL6 levels are elevated in skin tissues of individuals with mutations in PSORS6. Also, a recent report suggests significant association of ANGPTL6 gene polymorphisms (rs6511435) tends to be associated with a 20% higher risk of metabolic syndrome 39 , while another found that serum ANGPTL6 levels are significantly higher in subjects with metabolic syndrome than in healthy individuals 40 . Interestingly, psoriasis patients have a higher prevalence of metabolic syndrome 41 42 ; thus it would also be of interest to investigate whether there are ANGPTL6 gene polymorphisms associated with psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Tanigawa

Miyata

Tian

et al. 2016

Sci Rep

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Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility.

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“…For example, genes that have been related to the metabolic syndrome include angiopoietin-like 6 (ref. 33) on chromosome 19 (rs2116940, P =3.39 × 10 −6 ), growth differentiation factor 3 (ref. 34) on chromosome 12 (rs12307997, P =6.24 × 10 −7 ) and ubiquitin-like 5 (ref.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans

et al. 2013

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Hydrochlorothiazide (HCTZ) is one of the most widely prescribed antihypertensive medications. Although it is well known that HCTZ is associated with hyperglycemia and hypertriglyceridemia, the mechanisms underlying these adverse effects are not well understood. We performed a genome-wide association study and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses and the Genetic Epidemiology of Responses to Antihypertensive studies. Two single-nucleotide polymorphisms (rs12279250 and rs4319515 (r2=0.73)), located at 11p15.1 in the NELL1 gene, achieved genome-wide significance for association with change in fasting plasma triglycerides in African Americans, whereby each variant allele was associated with a 28 mg dl−1 increase in the change in triglycerides. NELL1 encodes a cytoplasmic protein that contains epidermal growth factor-like repeats and has been shown to represses adipogenic differentiation. These findings may represent a novel mechanism underlying HCTZ-induced adverse metabolic effects.

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Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study

Cited by 15 publications

References 19 publications

Angiopoietin-Like Proteins: A Comprehensive Look

Angiopoietin-Like Proteins: A Comprehensive Look

Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans

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