Non-dystrophic myotonia Chilean cohort with predominance of the SCN4A Gly1306Glu variant.

Non-dystrophic myotonias are a group of rare neuromuscular diseases linked to SCN4A or CLCN1. Among the subtypes, myotonia permanens, associated with the Gly1306Glu variant of SCN4A, is a relatively less frequent but more severe form. Most reports of non-dystrophic myotonias describe European populations. Therefore, to expand the genetic and phenotypic spectrum of this disorder, we evaluated 30 Chilean patients with non-dystrophic myotonias for associated variants and clinical characteristics. SCN4A variants were observed in 28 (93%) of patients, including 25 (83%) with myotonia permanens due to the Gly1306Glu variant. Myotonia permanens was inherited in 24 (96%) patients; the mean age of onset was 6 months, and the initial symptoms were orbicularis oculi myotonia in 17 (74%) patients and larynx myotonia in 12 (52%) patients. The extraocular muscles were involved in 11 (44%) patients, upper limbs in 20 (80%), and lower limbs in 21 (84%). Thirteen (52%) patients experienced recurrent pain and 10 (40%) patients reported limitations in daily life activities. Carbamazepine reduced myotonia in eight treated patients. The high frequency of the Gly1306Glu variant in SCN4A in Chilean patients suggests a founder effect and expands its phenotypic spectrum.

Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos / Association between cytochrome p4502c9 polymorphisms and losartan dosing in hypertensive patients

Background Losartan is widely used in many clinicals settings. Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Aims To identify the frequency of allelic variants CYP2C9*2 and CYP2C9*3 in hypertensive patients and to compare genotypes with a healthy Chilean population. To relate polymorphisms with the losartan dosing to obtain an optimal blood pressure. Material and Methods We studied 30 patients with controlled essential hypertension using losartan with normal liver function, and 202 healthy people. Peripheral blood DNA genotyping was performed by polymerase chain reaction to identify the polymorphisms. Allelic and genotypic frequencies were compared. Results In hypertensive patients, allelic frequencies were 0.85 (CYP2C9*1), 0.05 (CYP2C9*2) and 0.1 (CYP2C9*3). Genotypic frequencies were 73.3% (CYP2C9*1/*1), 6.7% (CYP2C9*1/*2), 16.7% (CYP2C9*1/*3) and 3.3% (CYP2C9*2/3); observing a significantly higher frequency of the allele CYP2C9*3 (p=0.041) and CYP2C9*1/*3 genotype (p=0.04). A non-significant tendency to need a larger dose of losartan was observed with the CYP2C9 * 3 allele, with an odds ratio (OR) of 1.46 (95% confidence intervals (CI) 0.01-18.64). The same tendency was observed with the need to use losartan twice a day, obtaining an OR of 5.88 (CI 0.54 -62.14). Conclusions There could be a relationship between the presence of CYP2C9 polymorphisms and the pathogenesis of hypertension. The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174.

[Association between cytochrome p4502c9 polymorphisms and losartan dosing in hypertensive patients]. / Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos.

Background Losartan is widely used in many clinicals settings. Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Aims To identify the frequency of allelic variants CYP2C9*2 and CYP2C9*3 in hypertensive patients and to compare genotypes with a healthy Chilean population. To relate polymorphisms with the losartan dosing to obtain an optimal blood pressure. Material and Methods We studied 30 patients with controlled essential hypertension using losartan with normal liver function, and 202 healthy people. Peripheral blood DNA genotyping was performed by polymerase chain reaction to identify the polymorphisms. Allelic and genotypic frequencies were compared. Results In hypertensive patients, allelic frequencies were 0.85 (CYP2C9*1), 0.05 (CYP2C9*2) and 0.1 (CYP2C9*3). Genotypic frequencies were 73.3% (CYP2C9*1/*1), 6.7% (CYP2C9*1/*2), 16.7% (CYP2C9*1/*3) and 3.3% (CYP2C9*2/3); observing a significantly higher frequency of the allele CYP2C9*3 (p=0.041) and CYP2C9*1/*3 genotype (p=0.04). A non-significant tendency to need a larger dose of losartan was observed with the CYP2C9 * 3 allele, with an odds ratio (OR) of 1.46 (95% confidence intervals (CI) 0.01-18.64). The same tendency was observed with the need to use losartan twice a day, obtaining an OR of 5.88 (CI 0.54 -62.14). Conclusions There could be a relationship between the presence of CYP2C9 polymorphisms and the pathogenesis of hypertension. The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174.