Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans

Itokawa, Masanari; Arai, Makoto; Kato, Shuhei; Ogata, Yoko; Furukawa, Aizo; Haga, Shukoh; Ujike, Hiroshi; Sora, Ichiro; Ikeda, Kazuhiko; Yoshikawa, Takeo

doi:10.1016/s0304-3940(03)00718-3

Cited by 68 publications

(75 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis of linkage disequilibrium (LD) showed that polymorphisms rs16147 and rs5574 were in high LD (D 0 = 1.0; r 2 = 0.944), confirming previous results (Skibola et al 2005). Because rs16147 is a promoter polymorphism with established effects on NPY gene expression (Itokawa et al 2003), we focused our results primarily on rs16147. Table 4 Polymorphism rs16147 in the NPY gene was associated with an increased effect of Po-husk treatment in lowering systolic BP (sBP).…”

Section: Resultssupporting

confidence: 84%

“…In accordance with this, numerous studies have observed that the rs16147 G allele increases NPY expression (Itokawa et al 2003;Shah et al 2009). Our results support a role for the NPY gene in modulating hypertension and implicate the rs16147 polymorphism in a magnified response to soluble fibre consumption on sBP, particularly in those homozygous for allele A.…”

Section: Discussionsupporting

confidence: 56%

“…It has been shown that a putative SP1 transcription factor-binding site within the rs16147 stretch of the NPY gene sequence is lost within the rs16147 A allele (Itokawa et al 2003), implying that this allele may demonstrate lower NPY expression levels. In accordance with this, numerous studies have observed that the rs16147 G allele increases NPY expression (Itokawa et al 2003;Shah et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have described polymorphisms in LEP (leptin), NPY and PYY genes, and these genetic variations have been related to their expression levels and plasma concentrations (Itokawa et al 2003;Hoffstedt et al 2002). Interestingly, these polymorphisms have also been associated with CVD risk factors, such as obesity (Torekov et al 2005;Ma et al 2005), plasma lipids (Salminen et al 2008) and BP (Ilveskoski et al 2008).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers

et al. 2012

View full text Add to dashboard Cite

The satiating effect of fibre consumption has been related to gut hormones, such as peptide YY and leptin. These peptides may also influence cardiovascular (CVD) risk biomarkers. Nevertheless, there is wide interindividual variation in metabolic responses to fibre consumption. The objective was to investigate differences in the effects of soluble fibre, in the form of Plantago ovata husk (Po-husk) treatment, on CVD risk biomarkers according to selected polymorphisms in genes related to satiety. The study was a multi-centred, double-blind, placebo-controlled, parallel and randomised trial in mildmoderate hypercholesterolaemic patients (age range: 43-67 years). Eight polymorphisms in three genes related to satiety (LEP, NPY and PYY) were identified in 178 participants; 88 patients in the placebo (microcrystalline cellulose 14 g/day) group and 90 in the Po-husk (14 g/day) group, which had added to a low-saturated-fat diet for 8 weeks. The CVD biomarkers measured included the following: lipid profile, blood pressure (BP), glucose, insulin, hs-CRP, oxidised LDL and IL-6. Relative to the placebo, Po-husk consumption lowered the plasma total cholesterol concentration by 3.3 % according to rs7799039 polymorphism in the LEP gene (p \ 0.05). Furthermore, the Po-husk reduced systolic BP (mean [95 % CI]) by -8 mmHg (-14.16; -1.90) and hs-CRP by 24.9 % in subjects with the AA genotype of the rs16147 polymorphism in the NPY gene (32 % of our total population; p \ 0.05), which remained significant after Bonferroni correction. In conclusion, polymorphisms in the LEP and NPY genes potentiate the response to Po-husk, particularly the effects on systolic BP and the hs-CRP plasma concentration.

show abstract

Section: Resultssupporting

confidence: 84%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers

et al. 2012

View full text Add to dashboard Cite

show abstract

“…These in vitro and transgenic studies consistently support the key roles of CAMKK2 in brain function, including neurodevelopment such as neurite outgrowth and cognitive function such as learning and memory. Finally, CAMKK2 regulates production of the appetite stimulating hormone neuropeptide Y, an important neuropeptide that has been found associated with schizophrenia, 36,37 further supporting the possible role of CAMKK2 in schizophrenia pathogenesis. These findings led us to hypothesize that CAMKK2 may be a risk gene for schizophrenia.…”

Section: Introductionmentioning

confidence: 74%

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene

Luo

Huang

et al. 2013

Mol Psychiatry

View full text Add to dashboard Cite

A resistance gene in disguise for schizophrenia?

Doi¹,

Itokawa²,

Hoshi³

et al. 2006

American J of Med Genetics Pt B

Self Cite

View full text Add to dashboard Cite

We examined the hypothesis that -485 T, a novel polymorphism in the promoter region of the neuropeptide Y gene which was shown to be associated with schizophrenia in our previous paper, confers susceptibility to the disease. For a case-control association study, 331 unrelated Japanese schizophrenics (S(1): milder cases in the previous study, n = 212; and S(2): additional severer cases, n = 119) and 199 unrelated normal controls were recruited. Contribution of -485 T to the risk and the severity of the illness was examined by (1) comparing the risk in each genotype in the general population, (2) testing correlations between the gene-dose of -485 T, and the severity of chronic outcome in S(2) assessed with the Positive and Negative Symptom Scale, and (3) comparing the distribution of age at onset in S(1) + S(2) among the three genotypes. -485 T was significantly associated with schizophrenia in S(1) + S(2). Significant negative correlations were observed between the gene-dose and the symptom assessment scores in all items. The homozygote of -485 T showed a second peak frequency in the late-onset group both in males and females, while the homozygote of the alternative allele showed a single peak in the early-onset group. The higher risk of schizophrenia in the heterozygote than in the homozygote of -485 T in the general population did not support the possibility of linkage disequilibrium with a susceptibility gene. -485 T most likely confers resistance but not susceptibility to schizophrenia. An interaction between a nuclear resistance gene and a presumptive pathogenic gene in the mitochondrial DNA was suggested.

show abstract

Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans

Cited by 68 publications

References 13 publications

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene

A resistance gene in disguise for schizophrenia?

Contact Info

Product

Resources

About