Association of CYP2C19 genotype with type 2 diabetes

Background: CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of commonly prescribed drugs such as omeprazole, diazepam, tolbutamide and propranolol. Its expression is regulated by the constitutive androstane receptor (CAR), involved in glucocorticoids synthesis. Since a number of crossliniks have been described for CYPs and some hormones, an association of CYP2C19 with type 2 diabetes is likely. Methods: Two groups were studied, 352 diagnosed with type 2 diabetes patients and 342 healthy volunteers form Mexico City. Both groups were tested for CYP2C19*2 and *3 alleles. We carried out an allelic discrimination using TaqMan assay for *2, and used FRET sensor and anchor probes for *3. Results: Ninety one percent of the subjects had the wild type allele, 9% have the *2 allele;no subject presented the *3 allele. The CYP2C19*2 allele is associated with type 2 diabetes (p = 0.012). Admixmap program was used to correct the admixture of this population and get the correlation. This was further confirmed in a linear model with a 67% power and by the method of Strom and Wienker for association on subjects within the mean range of Amerindian ancestry only (60%). Conclusion: Type 2 diabetes patients have significatly more *2 allele than healthy volunteers, more evident for the patients with the homocygous genotype.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis Potosí and León,México

This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants（6-12 years old） from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index（BMI） percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group（P 〈 0.05）.The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6（Hardy Weinberg equilibrium x^2= 3.16,P = 0.07）;Trp = 81.5 and Arg= 18.5（Hardy Weinberg equilibrium x^2 = 2.2,P = 0.14） for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found（P = 0.08）,children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40（95%CI,1.03-1.90,P =0.03） after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

A diabetic hypertension treatment program for the underserved in rural Dominican Republic

Background: Worldwide, diabetes and hypertension are leading causes of preventable end-organ disease. The prevalence of these diseases in the Dominican Republic is high and the end stage complications common. A treatment program utilizing modern protocols often thought too complex for the rural poor was initiated. Methods: With local government permission, a pilot study utilized Dominican physicians and local healthcare advocates (cooperadores) to obtain medical histories and physical exams as well as to determine healthcare needs specifically for type 2 diabetes and hypertension. A glycosylated hemoglobin (A1c) was used to identify and stratify diabetes patients. Blood pressure parameters per established standards were used to identify patients with hypertension. As indicated, pharmacotherapy was initiated (see treatment protocols), multiple forms of education and awareness building utilized, and a protocol-driven follow-up program maintained under weekly review. Results: In fifteen months, 1405 patients were screened, 229 type 2 diabetes patients, 59 pre-diabetes patients, and 98 hypertension patients were identified and enrolled for education, treatment, and follow-up. Normalization of blood pressure in hypertensives at 6 month follow-up was 78% and reduction of A1c values to <7.0 was 79.8%. Conclusion: Utilizing a best practice approach per internationally agreed-upon parameters has been shown here to be not only relevant but capable of improving outcomes in a developing world setting. A model incorporating standard of care, education, and integration of local resources as established suggests that further study is warranted to evaluate the long-term benefits as well as secondary outcomes of this approach to local populations.