Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity
- 299 Downloads
Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with metabolic diseases. Increased transcription efficiency was observed in −75A allele carriers compared to −75G allele homozygotes. +83C allele was associated with higher body mass index and waist-to-hip ratio in type II diabetes subjects. −75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL, creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels. Allele frequencies were 0.102 and 0.21, respectively, for −75A and +83T. −75G allele showed significant association with hypertension (P = 0.001). An association between +83C allele and obesity was observed (P = 0.040) and this allele also showed an association with hypertension in the presence of cardiovascular disease (P = 0.047). Moreover, +83T allele was associated with lower glycated hemoglobin values (P = 0.026). To our knowledge, there is no data associating this polymorphism with glycated hemoglobin. Furthermore, individuals carrying AT haplotype have lower risk for developing hypertension (P = 0.0002), while GT haplotype carriers present decreased risk to develop obesity comparing to GC haplotype (P = 0.025). APOA1 polymorphisms analysis may be a useful tool to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases, such as hypertension and obesity.
KeywordsAPOA1 polymorphisms Hypertension Obesity Glycated hemoglobin
This research was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES, Brazil) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil).
Conflict of interest statement
The authors declare that they have no conflict of interest related to the publication of this manuscript.
- 1.Prado RR, Nascimento AF, Souza MFM (2006) Brazil Health 2006: an analysis of the health situation in Brazil. Editora MS, BrasíliaGoogle Scholar
- 4.Eichenbaum-Voline S, Olivier M, Jones EL, Naoumova RP, Jones B, Gau B, Patel HN, Seed M, Betteridge DJ, Galton DJ, Rubin EM, Scott J, Shoulders CC, Pennacchio LA (2004) Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 24:167–174PubMedCrossRefGoogle Scholar
- 5.Mar R, Pajukanta P, Allayee H, Groenendijk M, Dallinga-Thie G, Krauss RM, Sinsheimer JS, Cantor RM, de Bruin TW, Lusis AJ (2004) Association of the APOLIPOPROTEIN A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia. Circ Res 94:993–999PubMedCrossRefGoogle Scholar
- 7.Garasto S, Rose G, Derango F, Berardelli M, Corsonello A, Feraco E, Mari V, Maletta R, Bruni A, Franceschi C, Carotenuto L, De Benedictis G (2003) The study of APOA1, APOC3 and APOA4 variability in healthy ageing people reveals another paradox in the oldest old subjects. Ann Hum Genet 67:54–62PubMedCrossRefGoogle Scholar
- 10.Ordovas JM, Corella D, Cupples LA, Demissie S, Kelleher A, Coltell O, Wilson PW, Schaefer EJ, Tucker K (2002) Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr 75:38–46PubMedGoogle Scholar
- 15.Pulkkinen A, Viitanen L, Kareinen A, Lehto S, Laakso M (2000) MspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease. Diabetes Care 23:791–795PubMedCrossRefGoogle Scholar
- 20.Ma YQ, Thomas GN, Ng MC, Critchley JA, Cockram CS, Chan JC, Tomlinson B (2003) Association of two apolipoprotein A-I gene MspI polymorphisms with high density lipoprotein (HDL)-cholesterol levels and indices of obesity in selected healthy Chinese subjects and in patients with early-onset type 2 diabetes. Clin Endocrinol (Oxf) 59:442–449CrossRefGoogle Scholar
- 21.Ramos LR, Toniolo J, Cendoroglo MS, Garcia JT, Najas MS, Perracini M, Paola CR, Santos FC, Bilton T, Ebel SJ, Macedo MB, Almada CM, Nasri F, Miranda RD, Goncalves M, Santos AL, Fraietta R, Vivacqua I, Alves ML, Tudisco ES (1998) Two-year follow-up study of elderly residents in S Paulo, Brazil: methodology and preliminary results. Rev Saude Publica 32:397–407PubMedCrossRefGoogle Scholar
- 24.(1999) Is fasting glucose sufficient to define diabetes? Epidemiological data from 20 European studies. The DECODE-study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis of Diagnostic Criteria in Europe. Diabetologia 42:647-654Google Scholar
- 32.Miller O (2003) Bioquímica do Sangue—Substâncias não-eletrolíticas. In: Miller O (2003) O Laboratório e os métodos de imagem para o clínico 5th edn. Editora Atheneu, São PauloGoogle Scholar
- 34.Emery AEH (1986) Methodology in medical genetics—an introduction to statistical methods. Longman, EdinburghGoogle Scholar