RESUMO
Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1.
RESUMO
BACKGROUND/AIMS: The common polymorphism in the FTO gene (rs9939609) has been associated with obesity, type 2 diabetes, and appetite regulation. The aim of this study was to evaluate possible associations of FTO rs9939609 with dietary factors in patients with type 2 diabetes. METHODS: This was a cross-sectional study of 236 patients with type 2 diabetes (age 60.0 ± 10.3 years; diabetes duration 12.7 ± 8.2 years; 53.4% females) who were genotyped for FTO rs9939609. Patients underwent clinical and laboratory evaluations and 3-day weighed diet records. Data on dietary intake were categorized as high or low, based on median values. RESULTS: The AA genotype in the FTO gene was positively associated with high fat (>34% energy; OR = 2.17; 95% CI 1.02-4.63) and low fiber intakes (<16 g/day; OR = 2.42; 95% CI 1.05-5.57), adjusted for gender, BMI, total energy intake, systolic blood pressure, and HbA1c. When gender was taken into account, AA females had higher fat (37.4 ± 5.3 vs. 32.6 ± 7.5 and 32.2 ± 6.2% energy; p = 0.005) and lower fiber intakes (12.4 ± 4.4 vs. 15.1 ± 6.3 and 16.7 ± 5.6 g/day; p = 0.023) than patients with TT and AT genotypes. Multiple logistic regression models confirmed female associations for high fat (OR = 9.73; 95% CI 2.12-44.66) and low fiber intakes (OR = 4.28; 95% CI 1.14-16.06; p < 0.05 for all models). CONCLUSIONS: Patients with type 2 diabetes, who were carriers of the AA genotype of the FTO rs9939609, had increased fat and decreased fiber consumption, independently of BMI.
Assuntos
Diabetes Mellitus Tipo 2/genética , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Polimorfismo Genético , Proteínas/genética , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) gene, especially the common rs9939609 (A/T) SNP, are associated with body mass index (BMI), diabetes, and metabolic syndrome (MetS). MetS is highly prevalent in patients with type 2 diabetes and has been associated with chronic diabetic complications. Therefore, the aim of this study was to evaluate possible associations of the scarcely investigated rs7204609 (C/T) polymorphism, as well as the rs9939609 (A/T) polymorphism, with MetS and chronic diabetic complications in type 2 diabetic patients from Southern Brazil. DESIGN: This was a cross-sectional study. PATIENTS AND METHODS: A total of 236 patients with type 2 diabetes (age: 60.0 ± 10.3 years; diabetes duration: 12.7 ± 8.2 years; 53.4% women) were genotyped for the FTO rs7204609 and rs9939609 polymorphisms (ABI PRISM 7000 Real-Time PCR System). Patients underwent clinical, laboratory, and nutritional evaluation. MetS was defined according to the 2009-Joint Interim Statement. RESULTS: Carriers of C allele of the rs7204609 polymorphism (CT/CC genotypes, n = 35) were at increased risk for the presence of MetS (odds ratio [OR] = 4.56; 95% CI: 1.04 to 19.9), elevated waist circumference (OR = 8.66; 95% CI: 1.12 to 66.7), BMI: ≥ 30 kg/m(2) (OR = 3.71; 95% CI: 1.71 to 8.02), and microalbuminuria (OR = 2.30; 95% CI: 1.08 to 4.88), adjusted for gender and diabetes duration (P < .05 for all models). The rs9939609 polymorphism was not associated with MetS, elevated waist circumference or BMI, or diabetic complications. Daily energy and nutrient intakes did not differ according to the presence of the polymorphisms. CONCLUSIONS: The C allele of the rs7204609 polymorphism in the FTO gene increased the chance for the presence of MetS, especially central obesity, and microalbuminuria, independently of energy and nutrient intakes in this sample of type 2 diabetic patients from Southern Brazil.