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Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects
Year:
2011
Source of publication :
obesity (source)
Authors :
יעקבסון, עמנואל
;
.
Volume :
19
Co-Authors:
Hunt, S.C., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Hasstedt, S.J., Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, United States
Xin, Y., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Dalley, B.K., Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, United States
Milash, B.A., Health Sciences Center, University of Utah School of Medicine, Salt Lake City, UT, United States
Yakobson, E., Agricultural Research Organization, Volcani Center, Institute of Animal Science, Bet-Dagan, Israel
Gress, R.E., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Davidson, L.E., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Adams, T.D., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Facilitators :
From page:
2241
To page:
2247
(
Total pages:
7
)
Abstract:
Neuropeptide Y (NPY) is an appetite hormone that acts centrally to control feeding behavior. The 5′ and exon 2 regions of NPY2R, one of five NPY receptor genes, have been weakly and inconsistently implicated with obesity. With the ATG start site of the gene at the beginning of exon 2, single-nucleotide polymorphisms (SNPs) across intron 1 may show stronger associations with obesity than expected. Two 5′ SNPs, three intron 1 SNPs, and one synonymous exon 2 SNP were genotyped on 2,985 white Utah subjects. Previously associated FTO, NPY, NPY1R, MC4R, PPARGC1A, OR7D4, and four NPFFR2 SNPs were also genotyped and related to BMI. One NPY2R 5′ SNP (rs12649641, P = 0.008), an exon 2 SNP (rs2880415, P = 0.009), and an intron 1 SNP (rs17376826, P = 7 × 10 -6) were each significantly associated with BMI. All three SNPs, plus FTO (rs9939609, P = 1.5 × 10 -6) and two NPFFR2 SNPs (rs4129733, P = 3.7 × 10 13 and rs11940196, 4.2 × 10 -10) remained significant in a multiple regression additive model. Diplotypes using the estimated haplotypes of NPY2R, NPFFR2, and MC4R were significantly associated with BMI (P = 1.0 × 10 -10, 3.2 × 10 -8, and 1.1 × 10 -4, respectively). Haplotypes of NPY2R, NPFFR2, and MC4R, plus the FTO SNP, explained 9.6% of the BMI variance. SNP effect sizes per allele for the four genes ranged from 0.8 to 3.5 kg/m 2. We conclude that haplotypes containing the rs17376826 SNP in intron 1 of NPY2R have strong associations with BMI, some NPFFR2 haplotypes are strongly protective against or increase risk of obesity, and both NPY2R and NPFFR2 play important roles in obesity predisposition independent of FTO and MC4R. © 2011 The Obesity Society.
Note:
Related Files :
adult
Body mass index
Female
Gene
Genetic Loci
Male
obesity
proteins
עוד תגיות
תוכן קשור
More details
DOI :
10.1038/oby.2011.239
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
20945
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:40
Scientific Publication
Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects
19
Hunt, S.C., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Hasstedt, S.J., Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, United States
Xin, Y., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Dalley, B.K., Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, United States
Milash, B.A., Health Sciences Center, University of Utah School of Medicine, Salt Lake City, UT, United States
Yakobson, E., Agricultural Research Organization, Volcani Center, Institute of Animal Science, Bet-Dagan, Israel
Gress, R.E., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Davidson, L.E., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Adams, T.D., Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects
Neuropeptide Y (NPY) is an appetite hormone that acts centrally to control feeding behavior. The 5′ and exon 2 regions of NPY2R, one of five NPY receptor genes, have been weakly and inconsistently implicated with obesity. With the ATG start site of the gene at the beginning of exon 2, single-nucleotide polymorphisms (SNPs) across intron 1 may show stronger associations with obesity than expected. Two 5′ SNPs, three intron 1 SNPs, and one synonymous exon 2 SNP were genotyped on 2,985 white Utah subjects. Previously associated FTO, NPY, NPY1R, MC4R, PPARGC1A, OR7D4, and four NPFFR2 SNPs were also genotyped and related to BMI. One NPY2R 5′ SNP (rs12649641, P = 0.008), an exon 2 SNP (rs2880415, P = 0.009), and an intron 1 SNP (rs17376826, P = 7 × 10 -6) were each significantly associated with BMI. All three SNPs, plus FTO (rs9939609, P = 1.5 × 10 -6) and two NPFFR2 SNPs (rs4129733, P = 3.7 × 10 13 and rs11940196, 4.2 × 10 -10) remained significant in a multiple regression additive model. Diplotypes using the estimated haplotypes of NPY2R, NPFFR2, and MC4R were significantly associated with BMI (P = 1.0 × 10 -10, 3.2 × 10 -8, and 1.1 × 10 -4, respectively). Haplotypes of NPY2R, NPFFR2, and MC4R, plus the FTO SNP, explained 9.6% of the BMI variance. SNP effect sizes per allele for the four genes ranged from 0.8 to 3.5 kg/m 2. We conclude that haplotypes containing the rs17376826 SNP in intron 1 of NPY2R have strong associations with BMI, some NPFFR2 haplotypes are strongly protective against or increase risk of obesity, and both NPY2R and NPFFR2 play important roles in obesity predisposition independent of FTO and MC4R. © 2011 The Obesity Society.
Scientific Publication
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