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Novel neuropeptide Y1 and Y5 receptor gene variants: associations with serum triglyceride and high‐density lipoprotein cholesterol levels
Author(s) -
Blumenthal JB,
Andersen RE,
Mitchell BD,
Seibert MJ,
Yang H,
Herzog H,
Beamer BA,
Franckowiak SC,
Walston JD
Publication year - 2002
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2002.620302.x
Subject(s) - endocrinology , medicine , neuropeptide y receptor , biology , adipocyte , ldl receptor , lipoprotein , receptor , adipose tissue , cholesterol , neuropeptide
Neuropeptide Y (NPY) appears to play a critical role in the integration of appetite and energy expenditure through NPY Y1 and Y5 receptor subtypes. Moreover, the NPY Y1 receptor is highly expressed on human adipocytes, where it inhibits lipolysis. The genes encoding these receptors are transcribed co‐ordinately in opposite directions from a common promoter in a region of chromosome 4 that has been previously linked to triglyceride and small low‐density lipoprotein (LDL) particle concentration. Therefore, the purpose of this investigation was to examine the relationship between polymorphisms in the genes encoding NPY Y1 and Y5 and the development of obesity and dyslipidemia. We screened the promoter and coding regions and identified four polymorphic variants. One of these, a cytosine to thymine (C→T) substitution in the untranslated region between the genes for NPY Y1 and Y5 (allele frequency 0.11), was significantly associated with both lower fasting triglyceride level (152 vs 125 mg/dl), and higher high‐density lipoprotein (HDL) concentrations (49 vs 45 mg/dl) (p < 0.01) in 306 obese subjects. Given the stimulatory effect of NPY on adipocyte lipoprotein lipase (LPL) activity, and the lack of association of other polymorphisms with serum lipid levels, we hypothesize that this is a gain‐in‐function polymorphism.