Common Leptin Receptor Polymorphisms do not Modify the Effect of Alcohol Ingestion on Serum Leptin Levels in a Controlled Feeding and Alcohol Ingestion Study
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Suite 705, MSC 8314, Bethesda, Maryland 20892, USA.Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 07/2005; 14(6):1576-8. DOI: 10.1158/1055-9965.EPI-05-0008
We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P > or = 0.26).
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ABSTRACT: As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake in healthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29+/-3.75 years, body mass index (BMI) 24.3+/-3.5, leptin at baseline 3.3+/-3.1 ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day 1 of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1,032 g of ethanol (median) consumed within the last 7 days, leptin levels 2.3 mg/ml. A placebo-controlled double-blind trial was performed. Leptin levels of blood samples were taken at baseline (t(1)), before ethanol intake (t(2)), when blood alcohol had reached its maximum (t(3)) and the morning after (t(4)). The oral dose of ethanol administered was 0.6 g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t(1)) (rs=0.85, p<0.0001) and follow-up (t(4)) (rs=0.768, p<0.0001). (b) Leptin levels for the placebo and the alcohol-consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann-Whitney U-test (p=0.669, p=1.0 and p=0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t(1) and t(4) were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.
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ABSTRACT: Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.