OBJECTIVETo assess the association of S447X mutation and Hind III polymorphism in the lipoprotein lipase gene with dyslipidemia of the metabolic syndrome in patients with essential hypertension.

METHODSA total of 983 patients were randomly selected from those with hypertension (diagnosed in the Community-based Comprehensive Studies on Prevention and Control of Hypertension Project in China) and those not treated with anti-hypertensive medications for at least in 2 weeks immediately before blood collection. Among them were 389 subjects with dyslipidemia and 594 subjects without dyslipidemia. The definition of dyslipidemia in patients with hypertension was used only when triglyceride or HDL-cholesterol was at abnormal level. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine Ser447stop mutation and Hind III polymorphism in LPL gene.

RESULTSLinkage disequilibrium between the two sites was observed, with three major haplotypes identified: H+S, H-S, and H-X. The LPL gene S447X mutation and H-X haplotype were significantly associated with dyslipidemia (OR=0.547, 95%CI: 0.348-0.859 for S447X mutation; OR=0.537, 95%CI: 0.328-0.880 for H-X haplotype) in male, both by themselves and after adjustment for age, body mass index, smoking, alcohol intake, systolic blood pressure, diastolic blood pressure, education and serum glucose. The LPL H- carriers and H-S haplotype were significantly associated with dyslipidemia (OR=0.575, 95%CI: 0.358-0.923) in female after multivariate adjustment. Moreover, compared with the H+S haplotype, the H-X haplotypes were associated with significantly lower TG and Log (TG/HDL-C) levels in both men and women, and with higher HDL-C levels in women; whereas no significant difference was observed between the H-S and H+S haplotype. Compared with the H-S haplotype, the H-X haplotypes had significant effect on the HDL-C levels in women.

CONCLUSIONThe LPL H-X haplotype was one of the protective factors of dyslipidemia of metabolic syndrome in hypertensive patients. It is significantly associated with low triglyceride, log triglyceride-to-HDL-cholesterol ratio and high HDL-cholesterol levels. S447X mutation does not explain all the effect associated with the Hind III polymorphism, although the effect on serum lipids associated with the H-X haplotype appeared to be mainly mediated by the S447X mutation. It is possible that some functional mutations in the LPL gene besides the S447X mutation are in linkage disequilibrium with the Hind III polymorphism.

Aged ; Cholesterol, HDL ; blood ; Dyslipidemias ; blood ; complications ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; Humans ; Hypertension ; complications ; Linkage Disequilibrium ; Lipoprotein Lipase ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Triglycerides ; blood

Objective: To explore the clinical characteristics of drug-resistant tuberculosis (TB) in children and to study the effectiveness of second-line anti-TB therapy for children and to examine the incidence of adverse drug reactions. Method: Retrospective research was conducted. The clinical records of children in West China Second Hospital diagnosed as drug-resistant TB from January 2010 to June 2014 were investigated.The clinical characteristics and risk factors were analyzed retrospectively. Treatment effect at discharge was examined as a short-term outcome indicator to evaluate the effectiveness of second-line anti-TB therapy and the incidence of adverse drug reactions. χ² test was used. Result: Forty-six patients were diagnosed as drug-resistant TB in 443 children infected with TB, with a 10.4% resistance rate. The 46 children included 26 male and 20 female patients, aged from one month and 28 days to 17 years and 5 months, with the average age (8.4±4.5) years, >7 to 14 years old patients as the biggest part(25 patients, 54.3%). Among the 46 children, 20 patients(43.5%)had close contact with TB patients, of whom 12 patients (60.0%) contacted with family members (including parents, brothers and sisters and grandparents living together) and 8 patients(40.0%) contacted with patients from outside family (such as relatives or neighbors). Moreover, 11 cases (23.9%) were under initial treatment and 35 cases (76.1%) were retreated.From 2010 to 2014, the number of cases of initial and retreated patients had no significant difference(0 and 1, 1 and 13, 4 and 7, 4 and 11, 2 and 3 cases, χ²=3.255, P=0.196). Among retreated patients, 31.4% (11/35) had irregular treatment before.Until discharge, the effective rate was 87.0% (40/46), while the incidence rate of adverse drug reaction was 10.9%(5/46). Conclusion The therapy for drug-resistant TB is effective and the incidence of adverse drug reaction is relatively low.