Analysis of Genetic Variations in the Resistin Gene Shows No Associations With Obesity in Women

Beckers, Sigri; Peeters, Armand V.; Freitas, Fenna de; Mertens, Ilse; Hendrickx, Jan-Jaap; Gaal, Luc F. Van; Hul, Wim Van

doi:10.1038/oby.2007.131

Cited by 21 publications

(22 citation statements)

References 21 publications

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“…Several genetic studies have focused on the possible association between resistin polymorphisms and phenotypes of obesity or IR. We previously reported that we found no association of SNPs in RETN with complex obesity in women (16). These results were in line with association studies in other populations (17,18).…”

Section: Introductionsupporting

confidence: 80%

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

Beckers

Freitas²,

Zegers³

et al. 2011

European Journal of Endocrinology

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Objective: In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. Design/methods: We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. Results: Mutation analysis identified five sequence variants in our patient populations:0 -UTR C100 A/G, T73T, IV3-61 C/A, and C78S. In our control population, we only found the 3 0 -UTR C87 G/A variant. We started functional experiments for the C78S mutation that was found in a 20-year-old obese male (body mass index (BMI)Z39.7 kg/m 2 ) and his obese mother (BMIZ31.9 kg/m 2 ). In vitro testing demonstrated that the mutation does not impair mRNA expression. We identified a 100-fold lower extracellular protein concentration for mutant resistin compared with WT levels using a resistin ELISA on cell culture medium (PZ4.87!10 K6 ). We also detected a decreased intracellular concentration for the mutant protein (tenfold lower relative levels, PZ0.007). The plasma resistin levels of the proband and his mother, however, did not differ significantly from lean control individuals. Conclusions: In conclusion, we identified the first missense mutation in resistin in a morbidly obese proband and his obese mother. Functional testing of the mutant protein suggests that the C78S mutant protein is degraded, possibly resulting in a decreased extracellular concentration, which may predispose to obesity. 164 927-936 European Journal of Endocrinology

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Section: Introductionsupporting

confidence: 80%

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

Beckers

Freitas²,

Zegers³

et al. 2011

European Journal of Endocrinology

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“…However, similar studies attempting to associate serum resistin levels or its natural SNP variants to insulin resistance, diabetes 2 or obesity in humans brought discontinuous results [7][8][9][10][11][12]. These discrepancy findings led to suggestion, that resistin could exhibit in humans other physiological functions than in rodents.…”

Section: Discussionmentioning

confidence: 98%

“…When considering resistin involvement in pathophysiology of obesity and diabetes mellitus 2 in humans, resistin studies have produced contradictory findings. Although some studies reported increase of resistin in obesity and diabetes type 2, most did not show correlation between resistin circulating levels and body mass index or insulin resist-ance [7][8][9][10]. This contrast could be caused by fact, that human and mouse RETN genes share only 53% homology, therefore their functions may differ between them [11] and other roles of RETN may exist in human.…”

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confidence: 91%

Relationship of resistin levels with endometrial cancer risk

Hlavna

Kohut²,

Lipková³

et al. 2011

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Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p < 0.01). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.

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“…Several groups suggested resistin levels and SNPs to be associated with obesity, insulin resistance, and type 2 diabetes (19,(101)(102)(103)(104)(105)(106). However, other groups failed to identify changes in resistin levels or SNPs in these conditions (107)(108)(109)(110)(111)(112)(113)(114). Although a clear function for resistin in glucose metabolism in humans is still lacking, data indicate that resistin has a role in inflammatory processes.…”

Section: Resistinmentioning

confidence: 99%

Adipokines and Insulin Resistance

Rabe¹,

Lehrke²,

Parhofer³

et al. 2008

Mol Med

689

480

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Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune systemthereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-α and interleukin-6, vaspin, and visfatin on insulin resistance. LRb is restricted to the hypothalamus, brainstem and key regions of the brain which control feeding, energy balance and glucose metabolism.c Effects likely to be mediated through inhibition of a yet-unknown protease.d Effects mediated through nicotinamide adenine dinucleotide biosynthetic activity.

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Analysis of Genetic Variations in the Resistin Gene Shows No Associations With Obesity in Women

Cited by 21 publications

References 21 publications

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance

Relationship of resistin levels with endometrial cancer risk

Adipokines and Insulin Resistance

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