Novel neuropeptide Y1 and Y5 receptor gene variants: associations with serum triglyceride and high-density lipoprotein cholesterol levels.

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.

Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women's Health and Aging Study II cohort.

OBJECTIVES: To determine whether polymorphic variation in the myostatin gene differentially influences the maintenance of muscle strength in older adults, and to find supportive evidence in a cohort of older women. DESIGN: Correlation study of polymorphic variation in a cohort of older women. SETTING: Representatively sampled older female population living in the eastern half of Baltimore, Maryland. PARTICIPANTS: Participants were 286 women, age 70 to 79. Of these, 81.1% were Caucasian, 18.8% were African American, and 0.2% were Asian or Hispanic. MEASUREMENTS: Overall strength was measured with a dynamometer and defined as the sum of the strongest measures of hip, knee, and grip strength on the dominant side. RESULTS: We identified or confirmed six myostatin polymorphic variants in the Women's Health and Aging Study II population. Of the polymorphisms, K153R is the most common, with an allele frequency of 0.19 in African Americans. Unadjusted mean strength by genotype suggested lower muscle strength in those African-American women with the R genotype compared with those with the K genotype (K/K: 72.50 +/- 13.9 kg (n = 39) vs K/R: 67.14 +/- 11.4 kg (n = 13) vs R/R: 63.1 +/- 11.3 kg (n = 3)). After adjustment for race in a linear regression model, the R genotype remained associated with lower strength levels (P = .04). Statistical significance decreased when body mass index and race were both added to the model (P = .09). CONCLUSIONS: Recognizing that small sample size in the study of genes of modest effect are unlikely to yield significant differences, these data suggest an association of the R153 allele with lower strength in high-functioning older women, which should be studied further in a larger cohort.