Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels

Abstract

High serum levels of total and LDL cholesterol are important risk factors in the development of atherosclerotic coronary artery disease. Cholesterol metabolism is affected by nutritional, environmental and genetic factors. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in the hypothalamic regulation of energy balance by stimulating food intake and favoring energy storage through increased lipoprotein lipase activity in white adipose tissue. As a part of ongoing study of the genetic basis of obesity, we screened the NPY gene for sequence variants. We report here the identification of a common Leu(7)-to-Pro(7) polymorphism in the signal peptide of NPY. Presence of this Pro(7) in NPY was associated with higher serum levels of total and LDL cholesterol in obese subjects participating in two independent Finnish and Dutch studies. Furthermore, normal-weight Finns with Pro(7) also had higher serum levels of total and LDL cholesterol than did subjects with Leu(7)/Leu(7), as analyzed in three subsequent determinations at 5-year intervals during a 10-year follow-up period. The NPY polymorphism was not associated with higher cholesterol levels in normal-weight Dutch. Our study provides evidence that NPY is linked to cholesterol metabolism and that the polymorphism producing Pro(7) in NPY is one of the strongest genetic factors identified thus far affecting serum cholesterol, particularly in obese subjects.

Neuropeptide Y gene functional polymorphism influences susceptibility to hypertension in Indian population

“…Previous analysis of the entire coding region of the NPY gene in Finnish and Dutch non-diabetic obese subjects revealed a significant association between the T1128C polymorphism and high serum total cholesterol and low-density lipoprotein levels. 17 More recently, the T1128C polymorphism has been reported to be associated with type-2 diabetes, 16,24 atherosclerosis 15 and coronary heart disease. 25 Furthermore, the NPY T1128C polymorphism has been reported to be associated with myocardial infarction and stroke in Swedish hypertensive patients.…”

“…15,25,26 Irreproducibility of positive findings has been a common criticism levelled at association studies investigating the common genetic basis of complex diseases. 22 The frequency of the Pro7 allele has been reported to be 0.08 in Finns, 0.03 in Dutchmen 17 and virtually absent in Japanese 28,29 and Koreans. 30 An extremely low frequency of Pro7 was observed in a Chinese population, 31 whereas Duan et al 32 failed to detect this allele in the same region.…”

“…14 The Pro7 allele of T1128C has shown association with increased blood pressure (BP), 15 carotid atherosclerosis 16 and increased cholesterol levels and BP in obese subjects. 16,17 Given the above information, we propose that the NPY gene is a candidate gene for hypertension. Few studies to date have examined the association between NPY polymorphisms and hypertension, and these studies are mainly restricted to the Dutch and Nordic populations.…”

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

“…NPY has also been demonstrated in islet cells and pancreatic nerve fibers [9]. Furthermore, a single nucleotide polymorphism (SNP) at rs16139 (T1128C) identified an amino acid substitution from Leucine (L) to Proline (P) (L7P) in the signal peptide [10]. The minor allele (P) correlated with elevated NPY levels in plasma [11] perhaps due to an increased biosynthesis [12] [13].…”

Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene and changes in serum lipids during a family-based counselling intervention among school-aged children with a family history of CVD

“…NPY genotypes were determined by PCR and restriction enzyme digestion (3) . The primers used were 5 0 -CCCGTCCGTTGAGCCTTCTG-3 0 and 5 0 -CGGTCCCGCG GTCCC-3 0 .…”