RESUMEN
BACKGROUND: Evidence is sparse about the genetic determinants of major lipids in Pakistanis. METHODS AND RESULTS: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). CONCLUSIONS: Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.
Asunto(s)
Metabolismo de los Lípidos/genética , Lípidos/sangre , Adulto , Anciano , Estudios de Casos y Controles , Europa (Continente) , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Trastornos del Metabolismo de los Lípidos/sangre , Trastornos del Metabolismo de los Lípidos/etnología , Trastornos del Metabolismo de los Lípidos/genética , Lípidos/genética , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Pakistán , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. METHODS AND RESULTS: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis. CONCLUSIONS: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.
Asunto(s)
Pueblo Asiatico/genética , Cromosomas Humanos Par 9 , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Estudios de Casos y Controles , Europa (Continente) , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etnología , Oportunidad Relativa , Pakistán , Fenotipo , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the success rate and complications of intraoperative Mitomycin-C in dacryocystorhinostomy (DCR) surgery. STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: Isra postgraduate institute of Ophthalmology, Al-Ibrahim Eye Hospital, Malir, Karachi, from January 2003 to December 2004. PATIENTS AND METHODS: This study included total 90 eyes of 90 patients fulfilling the inclusion criteria. The surgical procedure of external DCR done with intraoperative Mitomycin-C with a neurosurgical cottonoid soaked with 0.2 mg/ml. Mitomycin C was applied to the anastomosed flaps and osteotomy site for 10 minutes, without Silicon tube intubation. Surgery was done under local as well as general anesthesia. Patients were followed for 6 months. RESULTS: Out of 90 patients included in this study, only 2 patients complained of persistent epiphora after 6 months follow-up and were labeled as failed DCR. Remaining 88 had either no tearing or significant improvement of tearing after 6 months follow up and patent lacrimal system by syringing without pressure. Success rate in this procedure was 97.77% (p-value < 0.001). This study showed very high rate of success. Only complication noted was excessive nasal bleeding which was easily controlled. CONCLUSION: Intraoperative Mitomycin-C application in external DCR is safe, effective, cheap adjunct that helps to achieve good results of DCR surgery.