RESUMO
The association of Pre-B cell colony enhancing factor 1 (PBEF1) with obesity, together with its pro-inflammatory properties suggests that PBEF1 might be another crucial mediator that links inflammation with obesity and primary osteoarthritis (OA). We hypothesized that polymorphisms in PBEF1 may modify the risk of developing OA. Thus we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 and evaluated the association between the genetic variants and OA risk in a two-stage case-control study including 196 cases and 442 controls in the first stage and 143 cases and 238 controls in the second stage. In the first stage, two SNPs (rs4730153 and rs16872158) were found to be potentially associated with OA risk (P < 0.05), which were further confirmed in the second stage with similar effects. After combining the two stages, we found that rs4730153 was significantly associated with decreased risk of OA in an additive genetic model (P < 0.05), while rs16872158 showed increased risk of developing OA (P < 0.05). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and OA risk (Ptrend = 5.25 × 10(-5)). These findings indicate that genetic variants in PBEF1 gene may modify individual susceptibility to OA in the Chinese population.
Assuntos
Citocinas/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Nicotinamida Fosforribosiltransferase/genética , Osteoartrite do Joelho/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: PBEF1 and its polymorphisms may be important in the physiopathology of obesity. We hypothesized that polymorphisms in PBEF1 gene may modify body mass index (BMI). METHODS: Thus, we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 gene and evaluated the association between the genetic variants and BMI in a population-based study including 442 subjects in northern China. RESULTS: We found that the SNP rs3801267 was significantly associated with decreased BMI (P = 0.026 in additive model), while the other 2 SNPs (rs4730153 and rs16872158) showed a borderline significant association with decreased BMI (P = 0.068 and 0.060 in additive models). Combined analysis of these 3 SNPs showed a significant allele-dosage association between the number of variant alleles and decreased BMI (P trend = 0.007). CONCLUSIONS: These findings indicate that genetic variants in PBEF1 gene may modify individual BMI in the Chinese population.
