CNV analysis and mutation screening indicate an important role for the <i>NPY4R</i> gene in human obesity

Aerts, Evi; Beckers, Sigri; Zegers, Doreen; Hoorenbeeck, Kim Van; Massa, Guy; Verrijken, An; Verhulst, Stijn; Gaal, Luc F. Van; Hul, Wim Van

doi:10.1002/oby.21435

Cited by 31 publications

(28 citation statements)

References 34 publications

(44 reference statements)

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“…The first study of CNV in this region and association with BMI reported an inverse correlation: a higher gene copy number was associated with reduced BMI in an elderly Chinese cohort [ 5 ]. A similar correlation was subsequently confirmed in a German cohort [ 6 ] and a Belgian cohort of children and adolescents with obesity and healthy adults with normal weight [ 12 ]. However, in a study of young Chinese individuals no CNV was detected in the 10q11.22 region [ 13 ].…”

Section: Introductionsupporting

confidence: 66%

Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference

et al. 2018

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Multiple genetic studies have linked copy number variation (CNV) in different genes to body mass index (BMI) and obesity. A CNV on chromosome 10q11.22 has been associated with body weight. This CNV region spans NPY4R, the gene encoding the pancreatic polypeptide receptor Y4, which has been described as a satiety-stimulating receptor. We have investigated CNV of the NPY4R gene and analysed its relationship to BMI, waist circumference and self-reported dietary intake from 558 individuals (216 men and 342 women) representing a wide BMI range. The copy number for NPY4R ranged from 2 to 8 copies (average 4.6±0.8). Rather than the expected negative correlation, we observed a positive correlation between NPY4R copy number and BMI as well as waist circumference (r = 0.267, p = 2.65×10−7 and r = 0.256, p = 8×10−7, respectively). Each additional copy of NPY4R correlated with 2.6 kg/m2 increase in BMI and 5.67 cm increase in waist circumference (p = 3.3×10−7 and p = 1×10−6, respectively) for women. For men, there was no statistically significant correlation between CNV and BMI. Our results suggest that NPY4R genetic variation influences body weight in women, but the exact role of this receptor appears to be more complex than previously proposed.

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Section: Introductionsupporting

confidence: 66%

Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference

et al. 2018

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“…NPY4R is expressed in peripheral organs including the gastrointestinal tract, liver, pancreas, and heart [ 24 ]. The specific NPY4R agonist, BA-129 inhibits the proliferation of pancreatic cancer cells in vitro [ 25 ], and genetic and structural variations in NPY4R have been implicated in the pathogenesis of obesity [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

et al. 2017

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Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323–3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190–5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523–9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507–21.28; P = 0.010).

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“…A GWAS for BMI in a small Chinese population also identified a region near 10q11.22 associated with BMI (160). Subsequent studies in European populations confirmed this association, demonstrating the utility of screening for CNV in non-European populations to identify novel variants implicated in obesity (161). Currently, the role of rare and common CNV in obesity remains relatively unexplored; however, it is unlikely that the CNV explain a significant portion of the missing heritability of obesity (162).…”

Section: Filling In the Gaps Of Missing Heritabilitymentioning

confidence: 99%

Ethnic and population differences in the genetic predisposition to human obesity

2017

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SummaryObesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments.

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CNV analysis and mutation screening indicate an important role for the NPY4R gene in human obesity

Cited by 31 publications

References 34 publications

Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference

Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference

Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

Ethnic and population differences in the genetic predisposition to human obesity

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