Background/Aims: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism. Methods: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles. Results: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals presented high triglyceride levels, and 68.1% of patients showed high cholesterol levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPARγ2 gene was found in 86.3% of patients; the Ala/Ala variant was not observed in any patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ polymorphism of the adiponectin gene was found in 54.6% of patients. Conclusions: No association was found between lipid parameters and the relevant Pvull, Avall and Sstl polymorphisms. However, we did observe an association of the Pro12Ala and ADIPOQ polymorphisms with higher lipid levels, suggesting a close relationship between these factors.

1.
Berardinelli W: An undiagnosed endocrinometabolic syndrome: report of 2 cases. J Clin Endocrinol Metab 1954;14:193-204.
2.
Seip M, Trygstad O: Generalized lipodystrophy. Arch Dis Child 1963;38:447-453.
3.
Garg A, Fleckenstein JL, Peshock RM, Grundy SM: Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy. J Clin Endocrinol Metab 1992;75:358-361.
4.
Miranda DM, Wajchenberg BL, Calsolari MR, Aguiar MJ, Silva JM, Ribeiro MG, Fonseca C, Amaral D, Boson WL, Resende BA, De Marco L: Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome. Clin Endocrinol 2009;71:512-517.
5.
Fu M, Kazlauskaite R, Baracho MFP, Santos MG, Brandão-Neto J, Villares S, Celi FS, Wajchenberg BL, Shuldiner AR: Mutations in Gng3lg and AGPAT2 in Berardinelli-Seip congenital lipodystrophy and Brunzell syndrome: phenotype variability suggests important modifier effects. J Clin Endocrinol Metab 2004;89:2916-2922.
6.
Wajchenberg BL: Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000;21:697-738.
7.
Geloneze B, Tambascia MA, Pareja JC, Repetto EM, Magna LA, Pereira SG: Serum leptin levels after bariatric surgery across a range of glucose tolerance from normal to diabetes. Obes Surg 2001;11:693-698.
8.
Amri EZ, Bonino F, Ailhaud G, Abumrad NA, Grimaldi PA: Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J Biol Chem 1995;270:2367-2371.
9.
Wahli W, Braissant O, Desvergne B: Peroxisome proliferator-activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more. Chem Biol 1995;2:261-266.
10.
Cagatay P, Susleyici-Duman BS, Ciftci C: Lipoprotein lipase gene PvuII polymorphism serum lipids and risk for coronary artery disease: meta-analysis. Dis Markers 2007;23:161-166.
11.
Salazar LA, Hirata MH, Quintão ECR, Hirata RD: Lipid-lowering response of the HMG-CoA reductase inhibitor fluvastatin is influenced by polymorphism in the low-density lipoprotein receptor gene in Brazilian patients with primary hypercholesterolemia. J Clin Lab Anal 2000;14:125-131.
12.
Smart MC, Dedoussis G, Louizou E, Yannakoulia M, Drenos F, Papoutsakis C, Maniatis N, Humphries SE, Talmud PJ: APOE, CEPT and LPL genes show strong association with lipid levels in Greek children. Nutr Metab Cardiovasc Dis 2010;20:26-33.
13.
Prior SL, Jones DA, Gill GV, Bain SC, Stephens JW: Association of the adiponectin rs266729 C>G variant and coronary heart disease in the low risk ‘Golden Years' type 1 diabetes cohort. Diabetes Res Clin Pract Suppl 2011;91:e71-e74.
14.
Vasques AC, Rosado LE, Alfenas RCG, Geloneze B: Critical analysis on the use of the homeostasis model assessment (HOMA) indexes in the evaluation of the insulin resistance and the pancreatic beta cells functional capacity. Arq Bras Endocrinol Metab 2008;52:32-39.
15.
Hegele RA, Joy TR, Al-Attar SA, Rutt BK: Lipodystrophies: windows on adipose biology and metabolism. J Lipid Res 2007;48:1433-1444.
16.
Tavares V, Hirata RD, Rodrigues AC, Monte O, Salles JE, Scalissi N, Speranza AC, Hirata MH: Association between Pro12Ala polymorphism of the PPAR-γ2 gene and insulin sensitivity in Brazilian patients with type-2 diabetes mellitus. Diabetes Obes Metab 2005;7:605-611.
17.
Swarbrick MM, Chapman CM, McQuillan BM, Hung J, Thompson PL, Beilby JP: A Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 is associated with combined hyperlipidaemia in obesity. Eur J Endocrinol 2001;144:277-282.
18.
Beamer BA, Yen CJ, Andersen RE, Muller D, Elahi D, Cheskin LJ, Andres R, Roth J, Shuldiner AR: Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes 1998;47:1806-1808.
19.
Pihlajamäki J, Vanhala M, Vanhala P, Laakso M: The Pro12Ala polymorphism of the PPARγ2 gene regulates weight from birth to adulthood. Obes Res 2004;12:187-190.
20.
Sánchez JLG, Ríos MS, Pérez CF, Laakso M, Martínez Larrad MT: Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur J Endocrinol 2002;147:495-501.
21.
Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998;20:284-287.
22.
Badii R, Bener A, Zirie M, Al-Rikabi A, Simsek M, Al-Hamaq AO, Ghoussaini M, Froguel P, Wareham NJ: Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population. Acta Diabetol 2008;45:15-21.
23.
Frederiksen L, Brødbaek K, Fenger M, Jørgensen T, Borch-Johnsen K, Madsbad S, Urhammer SA: Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab 2002;87:3989-3992.
24.
Mancini FP, Vaccaro O, Sabatino L, Tufano A, Rivellese AA, Riccardi G, Colantuoni V: The Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes. Diabetes 1999;48:1466-1468.
25.
Rosmond R, Chagnon M, Bouchard C: The Pro12Ala PPARgamma2 gene missense mutation is associated with obesity and insulin resistance in Swedish middle-aged men. Diabetes Metab Res Rev 2003;19:159-163.
26.
Mori Y, Kim-Motoyama H, Katakura T, Yasuda K, Kadowaki H, Beamer BA, Shuldiner AR, Akanuma Y, Yazaki Y, Kadowaki T: Effect of the Pro12Ala variant of the human peroxisome proliferator-activated receptor gamma 2 gene on adiposity, fat distribution, and insulin sensitivity in Japanese man. Biochem Biophys Res Commun 1998;251:195-198.
27.
Oh EY, Min KM, Chung JH, Min YK, Lee MS, Kim KW, Lee MK: Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetes and obese subjects. J Clin Endocrinol Metab 2000;85:1801-1804.
28.
Salazar LA, Hirata MH, Forti N, Diament J, Giannini SD, Issa JS, Hirata RD: PvuII intron 15 polymorphism at the LDL receptor gene is associated with differences in serum lipid concentrations in subjects with low and high risk for coronary artery disease from Brazil. Clin Chim Acta 2000;293:75-88.
29.
Long XJ, Yin RX, Li KL, Liu WY, Zhang L, Cao XL, Miao L, Wu DF, Htet Aung LH, Hu XJ: Low density lipoprotein receptor gene AvaII polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Lipids Health Dis 2011;10:1-12.
30.
Humpheres S, King-Underwood L, Gudnason V, Seed M, Delattre S, Clavey V, Fruchart JC: Six DNA polymorphisms in the low density lipoprotein receptor gene: their genetic relationship and an example of their use for identifying affected relatives of patients with familial hypercholesterolaemia. J Med Genet 1993;30:273-279.
31.
Chhabra S, Narang R, Lakshmy R, Vasisht S, Agarwal DP, Srivastava LM, Manchanda SC, Das N: Apoliprotein C3 SstI polymorphism in the risk assessment of CAD. Mol Cell Biochem 2004;259:59-66.
32.
Rees A, Stocks J, Williams LG, Caplin JL, Jowett NI, Camm AJ, Galton DJ: DNA polymorphisms in the apolipoprotein C-III and insulin genes and atherosclerosis. Atherosclerosis 1985;58:269-275.
33.
Chhabra S, Agarwal DP, Vasisht S, Luthra K, Narang R, Manchanda SC, Srivastava LM, Das N: Study of apolipoprotein C3 Sstl polymorphism in healthy volunteers from Northern India. Indian J Clin Biochem 2003;18:34-38.
34.
Oguri M, Kato K, Yokoi K, Itoh T, Yoshida T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nishigaki Y, Tanaka M, Nozawa Y, Yamada Y: Association of genetic variants with myocardial infarction in Japanese individuals with metabolic syndrome. Atherosclerosis 2009;206:486-493.
35.
Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y: Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med 2008;21:801-808.
36.
Hoefle G, Muendlein A, Saely CH, Risch L, Rein P, Koch L, Schmid F, Aczel S, Marte T, Langer P, Drexel H: The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men. Thromb Haemost 2007;97:451-457.
37.
Zhang D, Ma J, Brismar K, Efendic S, Gu HF: A single nucleotide polymorphism alters the sequence of SP1 binding site in the adiponectin promoter region and is associated with diabetic nephropathy among type 1 diabetic patients in the Genetics of Kidneys in Diabetes Study. J Diabetes Complications 2009;23:265-272.
38.
Liu F, He Z, Deng S, Zhang H, Li N, Xu J: Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population. Mol Biol Rep 2011;38:1983-1988.
39.
Prior SL, Gable DR, Cooper JA, Bain SC, Hurel SJ, Humphries SE, Stephens JW: Association between the adiponectin promoter rs266729 gene variant and oxidative stress in patients with diabetes mellitus. Eur Heart J 2009;30:1263-1269.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.