Assuntos
Aminoidrolases/genética , Angiotensinas/genética , Apolipoproteínas/genética , Fator V/genética , Genes/genética , Estudos de Associação Genética/métodos , Variação Genética/genética , Humanos , Metanálise como Assunto , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Protrombina/genética , Acidente Vascular Cerebral/genéticaRESUMO
Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 x 10(-7)). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 x 10(-5)). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 +/- 10(-10)). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apolipoproteínas/genética , Artrite Reumatoide/genética , Estudos de Casos e Controles , DNA/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Heterozigoto , Homozigoto , Lipocalinas/genética , Luciferases/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de RiscoRESUMO
O objetivo do presente manuscrito foi revisar o possível papel dos lipídeos dietéticos na nefropatia diabética (ND), considerando as alterações do perfil lipídico associadas e a interação entre aspectos dietéticos e genéticos. Os lipídeos dietéticos podem ter um papel importante no desenvolvimento e na progressão da ND. A composição das gorduras da dieta tem sido associada com a ND, particularmente à microalbuminúria e às anormalidades lipídicas e de função endotelial. Entretanto, ainda não está comprovado o benefício da modificação da ingestão de gorduras em pacientes com ND, em especial sobre desfechos definitivos, como incidência e progressão da ND, insuficiência renal e morte. Além disso, a resposta do perfil lipídico à ingestão de gorduras pode ser influenciada por fatores genéticos. A identificação de polimorfismos genéticos específicos associados a essa interação poderá permitir a individualização de estratégias nutricionais na ND.
The aim of the present study was to review the possible role of dietary lipids in diabetic nephropathy (DN), taking into account associated abnormalities of serum lipids and interaction of dietary and genetic aspects. Dietary lipids may have an important role in the development and progression of DN. The fat diet composition has been associated with DN, particularly with microalbuminuria, serum lipids abnormalities, and endothelial function. However, the beneficial effect of fat intake modification for these patients is not fully established, especially regarding hard outcomes, such as DN incidence and progression, kidney failure, and death. Moreover, genetic factors may influence the response of serum lipids to fat intake. The identification of specific genetic polymorphisms associated with this interaction could allow adoption of individual nutritional strategies in DN.
Assuntos
Humanos , Dieta , Nefropatias Diabéticas/etiologia , Gorduras na Dieta/efeitos adversos , Lipídeos/sangue , Apolipoproteínas/genética , Colesterol/sangue , Nefropatias Diabéticas/dietoterapia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/fisiopatologia , Dieta/efeitos adversos , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ácidos Graxos/administração & dosagem , Variação Genética , Rim/efeitos dos fármacos , Lipídeos/genética , Polimorfismo Genético , Triglicerídeos/sangueRESUMO
Lipoprotein(a) [Lp(a)] is a complex lipoprotein particle in human plasma. It is composed of apolipoprotein B (Apo B)-100 and apolipoprotein(a) which are linked by a disulfide bond. Plasma levels of the Lp(a) vary greatly (over 1,000 folds) among individuals. Elevated plasma levels of the Lp(a) have been shown to be an independent risk factor for coronary artery diseases (CAD). The level of Lp(a) is controlled by a single gene, the Apo(a) gene, with multiple alleles; each encodes different concentrations of the Lp(a). Previous studies revealed the presence of polymorphisms in the 5'-flanking region (FL) of the Apo(a) gene at 3 positions: G or A (-914), C or T(-49), and G or A (-21), which can be detected by cleavage of PCR-amplified DNA products with TaqI, MaeII and HhaI, respectively. The 5'-FL genotypes of the Apo(a) gene can be classified by the combination of the presence (+) or absence (-) of these restriction sites into 5 types; type A, +++, type B, -++, type C, -+-, type D, --+ and type E, +-+. In the present study, the authors analyzed the 5' FL types of the Apo(a) gene by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 100 healthy control subjects, 26 CAD patients with [Lp(a)] < or = 30 mg/dL, and 94 CAD patients with [Lp(a)] > 30 mg/dL. The authors found that the genotype frequencies of the Apo(a) gene were 53, 16, 27 and 4%, for types A, B, C and D respectively in normal healthy controls. In CAD patients with [Lp(a)] < or = 30 mg/dL, the distribution of the genotype frequencies were 53.8, 11.5, 30.8 and 3.9% for types A, B, C and D, respectively. Additionally in CAD patients with [Lp(a)] > 30 mg/dL, the genotype frequencies were 60.6, 11.7, 21.3 and 6.4% for types A, B, C and D, respectively. The present study might shed some light to understand CAD at the molecular level.
Assuntos
Região 5'-Flanqueadora/genética , Adulto , Apolipoproteínas/genética , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Dislipidemias/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Polimorfismo Genético , Fatores de Risco , Tailândia/epidemiologiaRESUMO
Congenital generalized lipodystrophy is a rare inherited disease. One of its features is a disturbance in lipid metabolism characterized by hypercholesterolemia and hypertriglyceridemia. A brother and a sister with congenital generalized lipodystrophy, an 8-year old male and a 12-year old female were studied. The mother and a 6-year old brother were healthy. The genetic analysis of Sstl RFLP of the apo Al-CIII-AIV gene cluster showed the presence of the rare Sstl allele (S2) in the patients but not in the healthy mother and brother. As this uncommon allele has been reported to be related to high plasma triglyceride levels, this association could be relevant in explaining in part the hypertriglyceridemia observed in these patients.