Cardiovascular diseases are main cause of morbidity and mortality in acromegaly. Polymorphisms of FTO gene are associated with obesity and increased risk of CVD (independently of BMI). Aim of this study was to investigate the allele frequencies of two FTO gene polymorphisms: rs9939609 and rs9930506 in patients with acromegaly and to examine the association of FTO gene polymorphisms with BMI and selected metabolic parameters.
Identification of two single nucleotide polymorphisms of FTO gene was carried out in 51 patients with acromegaly using the minisequencing method.
The risk-allele frequencies of rs9939609 and rs9930506 polymorphisms were 0.471 and 0.529, respectively and they were higher than in general European population. There is no association of FTO gene polymorphisms with BMI, glucose, total cholesterol, LDL cholesterol and triglyceride. The risk alleles were associated with decreased HDL cholesterol concentration. Homozygotes for the rs9939609-risk allele had 1.25-fold lower HDL cholesterol concentration than carriers of the TT genotype (p = 0.0024). The estimated average decrease in HDL cholesterol concentration per risk allele for rs9930506 was 11.2%. Nevertheless, statistically significant differences were observed only between AG versus GG and AA versus GG genotypes. Homozygotes for the rs9930506-risk allele had 1.27-fold lower HDL cholesterol concentration than carriers of the AA genotype (p = 0.007).
The risk-allele frequencies of studied polymorphisms in acromegaly were higher than in general European population. There is an association between FTO gene polymorphisms and HDL cholesterol concentration, suggesting FTO gene polymorphisms may be associated with higher CVD risk in patients with acromegaly.
Bolanowski M, Ruchała M, Zgliczyński W, Kos-Kudła B, Bałdys-Waligórska A, Zieliński G, Bednarczuk T, Hubalewska-Dydejczyk A, Kamiński G, Marek B, Daroszewski J, Waśko R, Lewiński A (2014) Acromegaly—a novel view of the patient. Polish proposals for diagnostic and therapeutic procedures in the light of recent reports. Endokrynol Pol 65:326–331 CrossRefPubMed
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894 CrossRefPubMedPubMedCentral
Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orru M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR (2007) Genome-Wide Association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:1200–1210 CrossRef
Lappalainen T, Kolehmainen M, Schwab US, Tolppanen AM, Stančáková A, Lindström J, Eriksson JG, Keinänen-Kiukaanniemi S, Aunola S, Ilanne-Parikka P, Herder C, Koenig W, Gylling H, Kolb H, Tuomilehto J, Kuusisto J, Uusitupa M (2011) Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism—The Finnish Diabetes Prevention Study. Nutr Metab Cardiovasc Dis 21:691–698 CrossRefPubMed
Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O’Rahilly S, Schofield C (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate–dependent nucleic acid demethylase. Science 318:1469–1472 CrossRefPubMedPubMedCentral
Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C (2008) Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 15:23–24
Rosskopf D, Schwahn C, Neumann F, Bornhorst A, Rimmbach C, Mischke M, Wolf S, Geissler I, Kocher T, Grabe HJ, Nauck M, Hebebrand J, Kroemer HK, Friedrich N, Völzke H, Wallaschofski H (2011) The growth hormone - IGF-I axis as a mediator for the association between FTO variants and body mass index: results of the Study of Health in Pomerania. Int J Obes 35:364–372 CrossRef
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative centrifuge. Clin Chem 18:499–502 PubMed
Arking D, Chakravarti A (2009) Understanding cardiovascular disease through the lens of genome-wide assiociation studies. Cell Press 25(9):387–394
Turgut S, Topsakal S, Ata MT, Herek D, Akın F, Özkan Ş, Turgut G (2016) Leptin receptor gene polymorphism may affect subclinical atherosclerosis in patients with acromegaly. Med Biotechnol 8(3):145–150
Oguz E, Tabur S, Akbas H, Duzen IV, Karabag H, Akkafa F, Ozkaya M, Alasehirli B (2015) The association of ICAM E469K with cardiovascular characteristics of acromegaly. Eur Rev Med Pharmacol Sci 19:1673–1679 PubMed
International HapMap Project: ftp://ftp.ncbi.nlm.nih.gov/hapmap/. Accessed 12 May 2017
Zdrojowy-Wełna A (2017) Fat mass and obesity related (FTO) gene polymorphism in Lower Silesia population, and its relation to selected factors of cardiovascular risk (doctoral thesis, in Polish), Wroclaw
Freathy RM, Timpson NJ, Lawlor DA, Pouta A, Ben-Shlomo Y, Ruokonen A, Ebrahim S, Shields B, Zeggini E, Weedon MN, Lindgren CM, Lango H, Melzer D, Ferrucci L, Paolisso G, Neville MJ, Karpe F, Palmer CN, Morris AD, Elliott P, Jarvelin MR, Smith GD, McCarthy MI, Hattersley AT, Frayling TM (2008) Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes 57:1419–1426 CrossRefPubMedPubMedCentral
Circulation. Third Report of the National Cholesterol Education Program (NCEP) Exper Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III) Final Report. Internet: http://circ.ahajournals.org/content/106/25/3143.long. Accessed 20 July 2017
- Association between FTO gene polymorphisms and HDL cholesterol concentration may cause higher risk of cardiovascular disease in patients with acromegaly
- Springer US
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II