RESUMEN
BACKGROUND: Familial hypercholesterolemia (FH) is a monogenic disorder of lipoprotein metabolism leading to an increased risk of premature cardiovascular disease. Genetic testing for FH is not commonly used in Asian countries. We aimed to define the genetic spectrum of FH in Hong Kong and to test the feasibility of cascade genetic screening. METHODS: Ninety-six Chinese subjects with a clinical diagnosis of FH were recruited, and family-based cascade screening incorporating genetic testing results was performed. RESULTS: Forty-two distinct mutations were identified in 67% of the index FH cases. The majority of causative mutations were in the LDLR gene. The three commonest mutations in the LDLR gene were NM_000527.4(LDLR): c.1241 T>G, NM_000527.4(LDLR): c.1474G>A, and NM_000527.4(LDLR): c. 682G>A, and nine novel variants were identified. The NM_000384.2(APOB): c.10579 C>T variant of the APOB gene was found in 5% of the index subjects. The presence of causative mutation significantly increased the odds of successful family recruitment for screening with an OR of 3.7 (95% CI: 1.53-9.11, p = 0.004). CONCLUSION: Approximately two-third of the subjects in this clinically ascertained sample of patients with FH had a discrete genetic basis. Genetic identification improves the response rate and efficiency of family screening.
Asunto(s)
Frecuencia de los Genes , Hiperlipoproteinemia Tipo II/genética , Adulto , Anciano , Apolipoproteína B-100/genética , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptores de LDL/genéticaRESUMEN
Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.
Asunto(s)
Cromosomas Humanos Par 17/genética , Predisposición Genética a la Enfermedad , Parálisis Periódicas Familiares/genética , Sitios de Carácter Cuantitativo , Tirotoxicosis/genética , Adulto , Pueblo Asiatico/genética , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Parálisis Periódicas Familiares/etnología , Parálisis Periódicas Familiares/etiología , Polimorfismo de Nucleótido Simple/fisiología , Canales de Potasio de Rectificación Interna/genética , Sitios de Carácter Cuantitativo/genética , Sitios de Carácter Cuantitativo/fisiología , Tirotoxicosis/complicaciones , Tirotoxicosis/etnologíaRESUMEN
BACKGROUND: Autoimmune thyroid disease (AITD) often coexists with pernicious anemia (PA) among whites. The study aimed to determine thyroid autoimmunity in Chinese patients with PA. METHODS: From the data of a hospital-based longitudinal study of Chinese PA patients (1994-2007), those with complete information of antibodies to thyroid peroxidase (TPO), thyroglobulin (Tg), and gastric parietal cell; serum thyroid-stimulating hormone and free thyroxine; gastric mucosal histology; and family history of AITD were analyzed. RESULTS: Among 126 Chinese PA patients, 44% had TPO/Tg antibodies and 13.5% AITD. TPO/Tg antibodies occurred in 33% (16 of 49) of male and 52% (40 of 77) of female patients (P = 0.034). Graves disease (8 patients) tended to antedate PA and was associated with no or low titers of TPO/Tg antibodies. Primary hypothyroidism (9 patients) developed during follow-up and was associated with high TPO/Tg antibody titers. The TPO/Tg antibodies did not affect the clinical course of PA but was associated with an enhanced risk of developing AITD and vitiligo. Overall, AITD (before and after PA) occurred in 23% (13 of 56) and 5.7% (4 of 70) of PA patients with and without antibodies (P = 004). During follow-up (mean duration of 75.24 +/- 46.39 months), 10 patients developed AITD-7 new onset of hypothyroidism and 3 progression/relapse of prior AITD. Logistic regression analysis of presenting features of PA revealed 2 independent factors for AITD development during follow-up-presence of thyroid antibodies (odds ratio 20.2, 95% confidence interval 1.8-223) and history of prior AITD (odds ratio 39.8, 95% confidence interval 2.3-679). CONCLUSION: It is recommended to screen thyroid antibodies and monitor thyroid function during follow-up.
