Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians

C. P. Jenkinson, K. Cray, K. Walder, H. Herzog, R. Hanson, E. Ravussin

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

OBJECTIVE: To investigate whether the neuropeptide Y receptor 5 gene (NPY5R) is associated with obesity in humans. DESIGN: The NPY5R gene was screened for polymorphisms by direct sequencing in two groups of Pima Indians, selected for extremes of body mass index (BMI). Genotype frequencies were analyzed for association with BMI extreme. SUBJECTS: Full-heritage Pima Indians, non-diabetic and not first degree relatives. Obese group: 19 M/24 F, BMI = 49 ± 7 kg/m2 (mean ± s.d.) age = 24 ± 2 y, lean group: 16 M/16 F, BMI = 23 ± 2 kg/m2, age = 27 ± 3 y. MEASUREMENTS: Initially, the entire gene (proximal promoter, exon 1A, coding sequence, 5' and 3' UTRs) was sequenced in a subset of 20 individuals. No variants were found in the coding sequence, however three novel single nucleotide polymorphisms were detected in the non-coding regions: (1) a C→T transition located within the promoter 28 bp upstream of the exon 1A transcription start site; (2) a T→C transition 94 bp downstream of the stop codon; and (3) a G→A transition 432 bp downstream of the stop codon. The polymorphisms were then screened in all 75 subjects. RESULTS: The polymorphisms had mean heterozygosities of 0.34-0.50 and were in strong linkage disequilibrium (P < 0.001). Genotype frequencies differed significantly in lean and obese Pimas for P2 (P = 0.04) and for a triple haplotype (P = 0.02, Bonferroni corrected). CONCLUSION: Considering the importance of this gene in regulation of body weight, the association of these polymorphisms with extremes of BMI in Pima Indians indicates that NPY5R, or a locus nearby, may contribute to susceptibility to obesity in this population.

Original languageEnglish (US)
Pages (from-to)580-584
Number of pages5
JournalInternational Journal of Obesity
Volume24
Issue number5
StatePublished - 2000
Externally publishedYes

Fingerprint

Neuropeptide Y Receptors
Potassium Iodide
neuropeptide Y
body mass index
Body Mass Index
obesity
Obesity
genetic polymorphism
receptors
Terminator Codon
stop codon
Genes
exons
Exons
genes
Genotype
promoter regions
genotype
5' Untranslated Regions
Transcription Initiation Site

Keywords

  • Association
  • Feeding
  • NPY
  • NPY5R
  • Obesity
  • Polymorphisms

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

Jenkinson, C. P., Cray, K., Walder, K., Herzog, H., Hanson, R., & Ravussin, E. (2000). Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. International Journal of Obesity, 24(5), 580-584.

Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. / Jenkinson, C. P.; Cray, K.; Walder, K.; Herzog, H.; Hanson, R.; Ravussin, E.

In: International Journal of Obesity, Vol. 24, No. 5, 2000, p. 580-584.

Research output: Contribution to journalArticle

Jenkinson, CP, Cray, K, Walder, K, Herzog, H, Hanson, R & Ravussin, E 2000, 'Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians', International Journal of Obesity, vol. 24, no. 5, pp. 580-584.
Jenkinson CP, Cray K, Walder K, Herzog H, Hanson R, Ravussin E. Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. International Journal of Obesity. 2000;24(5):580-584.
Jenkinson, C. P. ; Cray, K. ; Walder, K. ; Herzog, H. ; Hanson, R. ; Ravussin, E. / Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. In: International Journal of Obesity. 2000 ; Vol. 24, No. 5. pp. 580-584.
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AB - OBJECTIVE: To investigate whether the neuropeptide Y receptor 5 gene (NPY5R) is associated with obesity in humans. DESIGN: The NPY5R gene was screened for polymorphisms by direct sequencing in two groups of Pima Indians, selected for extremes of body mass index (BMI). Genotype frequencies were analyzed for association with BMI extreme. SUBJECTS: Full-heritage Pima Indians, non-diabetic and not first degree relatives. Obese group: 19 M/24 F, BMI = 49 ± 7 kg/m2 (mean ± s.d.) age = 24 ± 2 y, lean group: 16 M/16 F, BMI = 23 ± 2 kg/m2, age = 27 ± 3 y. MEASUREMENTS: Initially, the entire gene (proximal promoter, exon 1A, coding sequence, 5' and 3' UTRs) was sequenced in a subset of 20 individuals. No variants were found in the coding sequence, however three novel single nucleotide polymorphisms were detected in the non-coding regions: (1) a C→T transition located within the promoter 28 bp upstream of the exon 1A transcription start site; (2) a T→C transition 94 bp downstream of the stop codon; and (3) a G→A transition 432 bp downstream of the stop codon. The polymorphisms were then screened in all 75 subjects. RESULTS: The polymorphisms had mean heterozygosities of 0.34-0.50 and were in strong linkage disequilibrium (P < 0.001). Genotype frequencies differed significantly in lean and obese Pimas for P2 (P = 0.04) and for a triple haplotype (P = 0.02, Bonferroni corrected). CONCLUSION: Considering the importance of this gene in regulation of body weight, the association of these polymorphisms with extremes of BMI in Pima Indians indicates that NPY5R, or a locus nearby, may contribute to susceptibility to obesity in this population.

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