Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Abstract

Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and ε2/ε3/ε4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (ε2, ε3 and ε4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of ε2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/ 107 (6.5%); P < 0.05]. Therefore, our results suggest that the ε2 allele/ APOE might be a risk factor for diabetes in the Brazilian population.

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

“…To our knowledge, there is only one study (Errera et al 2006) that reported a higher frequency of E2 allele in the small number of male and female diabetic patients (type 1 and type 2) of African-Brazilian and European-Brazilian origins (Errera et al 2006). Unfortunately, this study (Errera et al 2006) did not evaluate the effects of sex and age in order to confirm the association between E2 allele and diabetes. Although E2 might be protective against the development of AD (Farrer et al 1997), it could be detrimental for T2D.…”

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

“…The control group was provided by the Biobank of our institute, and consisted of 401 individuals (336 individuals ascertained in São Paulo and 65 from Fortaleza-CE, as detailed in Errera et al [2006] and Orabona et al [2009], respectively). Ethical issues prevented the collection of control samples in other locations.…”

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry

“…Among them, 443 were EA (Portuguese, Spanish, Italian, and German) descendants and 124 AfA (West Africa, Angola, Mozambique) descendents (11,12). Patients were evaluated using a questionnaire, physical examination and laboratory tests.…”

“…The reference group (control) consisted of 190 healthy DM2-free blood donor volunteers at HC-USP (96 EA and 94 AfA, age: 48.28 ± 16.39 years), who were previously described by Errera et al (11,12). The main clinical and laboratory data are reported in Table 1 and were obtained as recommended previously (11,12). A group of 439 non-diabetic quilombo remnant individuals was also included.…”