Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits.

Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular filtration and electrolyte imbalance. Its economic impact on public health is challenging. Mexico has a high prevalence of CKD that is strongly associated with some of the most common metabolic disorders like diabetes and hypertension. The gradual loss of kidney functions provokes an inflammatory state and endocrine alterations affecting several systems. High serum levels of prolactin have been associated with CKD progression, inflammation, and olfactory function. Also, the nutritional status is altered due to impaired renal function. The decrease in calorie and protein intake is often accompanied by malnutrition, which can be severe at advanced stages of the disease. Nutrition and olfactory functioning are closely interconnected, and CKD patients often complain of olfactory deficits, which ultimately can lead to deficient food intake. CKD patients present a wide range of deficits in olfaction like odor discrimination, identification, and detection threshold. The chronic inflammatory status in CKD damages the olfactory epithelium leading to deficiencies in the chemical detection of odor molecules. Additionally, the decline in cognitive functioning impairs the capacity of odor differentiation. It is not clear whether peritoneal dialysis and hemodialysis improve the olfactory deficits, but renal transplants have a strong positive effect. In the present review, we discuss whether the olfactory deficiencies caused by CKD are the result of the induced inflammatory state, the hyperprolactinemia, or a combination of both.

High Iodine and Salt Intakes and Obesity do not Modify the Thyroid Function in Mexican Schoolchildren.

Mexico is considered as a nutritional transition country with a high prevalence of overweight and obesity, and recent studies have reported a high iodine intake in children. Both high iodine intake and obesity have been associated with thyroid dysfunction. Our aim was to assess iodine and salt intake and thyroid function in Mexican schoolchildren with normal weight and obesity. A cross-sectional study was performed during 2012-2013 in schoolchildren from Queretaro, Mexico. Six hundred seventy-eight schoolchildren were evaluated to obtain nutrition status, urinary iodine concentration (UIC) and thyroid volume (TVol). The prevalence of overweight and obesity was 47.3 %, the median UIC was 428 µg/L and TVol was normal in all schoolchildren; however, obese girls had a higher TVol than normal weight at the age of 8, 10 and 12 years. A subsample of schoolchildren was divided in 6-8 and 9-12-year-old groups, in order to compare thyroid function (thyrotropin, free T4, and anti-thyroid antibodies); iodine and salt intake were estimated with 24-h urinary samples. No differences in thyroid function were observed in both age groups. In the 6-8-year-old group, obese schoolchildren had higher iodine intake than normal-weight children (415.5 vs. 269.1 µg/day, p < 0.05), but no differences in salt intake. In contrast, in the 9-12-year-old group, obese schoolchildren had higher salt intake than normal-weight children (6.2 vs. 3.8 g/day, p < 0.05), but no differences in iodine intake. Dietary patterns could explain the differences between both age groups. Further studies are needed to identify the main sources of iodine intake in Mexican populations.

Iodine nutrition and thyroid function assessment in childbearing age women from Queretaro, Mexico.

OBJECTIVE: To assess iodine nutrition and thyroid function in Mexican childbearing age women. METHODS: 101 childbearing age women (21.7 ± 3.5 years) randomly selected from the university student population participated in this cross-sectional study. TSH, thyroid hormones, anti-thyroid antibodies, thyroid volume, iodine intake, and urinary iodine concentration (UIC) were assessed. The knowledge about the importance of iodine in nutrition was also evaluated by using questionnaires. RESULTS: TSH median (interquartile range) value was 1.9 (1.4-2.5) mIU/L, while FT4 median value was 9.0 (8.3- 9.6) µg/dL. The median FT3 and total rT3 values were 3.3 pg/mL and 40.1 ng/dL, respectively. The prevalence of subclinical hypothyroidism (serum TSH >4.5 mIU/L) and of positive anti-thyroid antibodies were 2.9% and <5.9%, respectively. Median thyroid volume was 5.6 mL and none of the subjects were diagnosed with goiter. Median urinary iodine concentration was 146 (104-180) µg/L. As for the knowledge of iodine nutrition, only 37.6% considered that a pregnant woman needs more dietary iodine than a non pregnant woman, while 43.6% recognized that the lack of iodine can cause mental retardation in children. CONCLUSIONS: Prevalence of thyroid test function abnormalities was low in this population and the median UIC indicates adequate iodine intake. We also found a poor knowledge about the importance iodine nutrition in the studied population.

Iodine nutrition and thyroid function assessment in child bearing age women from Queretaro, Mexico / Estado nutricio en yodo y función tiroidea en mujeres en edad reproductiva de Querétaro, México

Objective: To assess iodine nutrition and thyroid function in Mexican childbearing age women. Methods: 101 childbearing age women (21.7 ± 3.5 years) randomly selected from the university student population participated in this cross-sectional study. TSH, thyroid hormones, anti-thyroid antibodies, thyroid volume, iodine intake, and urinary iodine concentration (UIC) were assessed. The knowledge about the importance of iodine innutrition was also evaluated by using questionnaires. Results: TSH median (interquartile range) value was1.9 (1.4-2.5) mIU/L, while FT4 median value was 9.0 (8.3-9.6) μg/dL. The median FT3 and total rT3 values were 3.3pg/mL and 40.1 ng/dL, respectively. The prevalence of subclinical hypothyroidism (serum TSH >4.5 mIU/L) and of positive anti-thyroid antibodies were 2.9% and <5.9%,respectively. Median thyroid volume was 5.6 mL and none of the subjects were diagnosed with goiter. Median urinary iodine concentration was 146 (104-180) μg/L. As for the knowledge of iodine nutrition, only 37.6% considered that a pregnant woman needs more dietary iodine than a non pregnant woman, while 43.6% recognized that the lack of iodine can cause mental retardation in children. Conclusions: Prevalence of thyroid test function abnormalities was low in this population and the median UIC indicates adequate iodine intake. We also found a poor knowledge about the importance iodine nutrition in the studied population (AU)

Objetivo: Evaluar el estado nutricional en yodo y la función tiroidea en mujeres mexicanas en edad reproductiva. Métodos: 101 mujeres universitarias en edad reproductiva(21,7 ± 3,5 años) fueron seleccionadas al azar para participar en este estudio transversal. Se evaluaron los niveles séricos de tirotropina, hormonas tiroideas, anticuerpos anti-tiroideos, volumen tiroideo, consumo de yodo y yoduria. También se evaluó el conocimiento sobre la importancia del yodo en la nutrición. Resultados: La mediana (rango intercuartilar) de tirotropina fue de 1,9 (1,4-2,5) mIU/L, mientras que para T4libre fue de 9,0 (8,3-9,6) μg/dL. Los valores de la mediana de T3 libre y T3 reversa fueron de 3,3 pg/mL y 40,1 ng/dL, respectivamente. La prevalencia de hipotiroidismo subclínico fue 2,9% (tirotropina sérica >4,5 mUI/L). La prevalencia de anticuerpos antitiroideos positivos fue <5,9%.La mediana del volumen tiroideo fue de 5,6 mL y no se diagnosticaron mujeres con bocio. La mediana (rangointercuartilar) de la yoduria fue de 146 (104-180) μg/L. En cuanto al conocimiento de la importancia del yodo en la nutrición, el 37,6% consideró que las mujeres gestantes requieren más yodo en la dieta que las no gestantes, mientras que el 43,6% reconoció que la deficiencia de yodo puede causar retraso mental en los infantes. Conclusiones: Se encontró una baja prevalencia de alteraciones en las pruebas de función tiroidea, mientras que la mediana de la yoduria indicó un adecuado consumo de yodo. También se encontró un conocimiento bajo acerca de la importancia del yodo en la nutrición (AU)

Iodine nutrition in elementary state schools of Queretaro, Mexico: correlations between urinary iodine concentration with global nutrition status and social gap index.

OBJECTIVE AND METHODS: To estimate median urinary iodine concentration (UIC), and to correlate it with global nutrition indicators and social gap index (SGI) in 50 elementary state schools from 10 municipalities in the State of Queretaro, Mexico. RESULTS: 1,544 students were enrolled and an above of requirements of iodine intake was found (median UIC of 297 µg/L). Iodine status was found as deficient, adequate, more than adequate and excessive in 2, 4, 19 and 25 schools, respectively. Seventy seven percent of table salt samples showed adequate iodine content (20-40 ppm), while 9.6% of the samples had low iodine content (< 15 ppm). Medians of UIC per school were positively correlated with medians of body mass index (BMI) by using the standard deviation score (SDS) (r = 0.47; p < 0.005), height SDS (r = 0.41; p < 0.05), and overweight and obesity prevalence (r = 0.41; p < 0.05). Medians of UIC per school were negatively correlated with stunting prevalence (r = -0.39; p = 005) and social gap index (r = -0.36; p < 0.05). Best multiple regression models showed that BMI SDS and height were significantly related with UIC (p < 0.05). CONCLUSIONS: There is coexistence between the two extremes of iodine intake (insufficient and excessive). To our knowledge, the observed positive correlation between UIC and overweight and obesity has not been described before, and could be explained by the availability and consumption of snack food rich in energy and iodized salt.

Iodine nutrition in elementary state schools of Queretaro, Mexico: correlations between urinary iodine concentration with global nutrition status and social gap index / Consumo de iodo em escolas de ensino fundamental de Querétaro, México: correlação entre a concentração urinária de iodo, o estado nutricional geral e o índice de desigualdade social

OBJECTIVE AND METHODS: To estimate median urinary iodine concentration (UIC), and to correlate it with global nutrition indicators and social gap index (SGI) in 50 elementary state schools from 10 municipalities in the State of Queretaro, Mexico. RESULTS: 1,544 students were enrolled and an above of requirements of iodine intake was found (median UIC of 297 µg/L). Iodine status was found as deficient, adequate, more than adequate and excessive in 2, 4, 19 and 25 schools, respectively. Seventy seven percent of table salt samples showed adequate iodine content (20-40 ppm), while 9.6% of the samples had low iodine content (< 15 ppm). Medians of UIC per school were positively correlated with medians of body mass index (BMI) by using the standard deviation score (SDS) (r = 0.47; p < 0.005), height SDS (r = 0.41; p < 0.05), and overweight and obesity prevalence (r = 0.41; p < 0.05). Medians of UIC per school were negatively correlated with stunting prevalence (r = -0.39; p = 005) and social gap index (r = -0.36; p < 0.05). Best multiple regression models showed that BMI SDS and height were significantly related with UIC (p < 0.05). CONCLUSIONS: There is coexistence between the two extremes of iodine intake (insufficient and excessive). To our knowledge, the observed positive correlation between UIC and overweight and obesity has not been described before, and could be explained by the availability and consumption of snack food rich in energy and iodized salt.

OBJETIVO E MÉTODOS: Estimar a concentração de iodo urinário (CIU) mediana e correlacioná-la com os indicadores de nutrição geral e com o índice de desigualdade social (IDS) de 50 escolas estaduais de ensino fundamental de 10 municípios do estado de Querétaro, no México. RESULTADOS: Utilizou-se um total de 1.544 crianças e encontrou-se uma ingestão acima das necessidades de iodo (CIU mediana de 297 µg/L). O nível de iodo determinado foi deficiente, adequado, mais do que adequado e excessivo em 2, 4, 19 e 25 escolas, respectivamente. Setenta e sete por cento de amostras de sal de mesa mostraram uma quantidade de iodo adequada (20-40 ppm), enquanto 9,6% das amostras tinham um teor de iodo baixo (< 15 ppm). As medianas de CIU por escola foram correlacionadas positivamente com as medianas do índice de massa corporal (IMC) usando o desvio-padrão da contagem (DP) (r = 0,47; p < 0.005), o DP da altura (r = 0,41; p < 0.05) e a prevalência de sobrepeso e de obesidade (r = 0,41; p < 0,05). As medianas de CUI por escola foram correlacionadas negativamente com a prevalência de desnutrição (r = -0.39; p = 005) e com o índice de desigualdade social (r = -0.36; p < 0,05). Os melhores modelos de regressão múltipla mostraram que a DP do IMC e a altura foram relacionados significativamente com a CIU (p < 0,05). CONCLUSÃO: Existe uma convivência entre os dois extremos de ingestão de iodo (insuficiente e excessiva). Em nosso conhecimento, a correlação positiva entre a CIU, o excesso de peso e a obesidade não foi descrita anteriormente e poderia ser explicada pela disponibilidade e consumo de alimentos ou refeições ricos(as) em energia e sal iodado.

Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis.

BACKGROUND: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. METHODS: We studied 36 young Hispanic adults without diabetes (ages 18-40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. RESULTS: Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. CONCLUSIONS: Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.

Importance of iodine in pregnancy

Iodine is an essential constituent of thyroid hormones (TH). TH actively take part in critical periods of brain development during embryonic, fetal and postnatal stages. Therefore the absence of TH or iodine in these critical periods produces an irreversible brain damage. In fact, it is known that iodine deficiency is the leading cause of preventable brain damage worldwide. Because of the physiological adjustments during pregnancy iodine requirements increase significantly from 150 μg per day in non-pregnant adult women to 250 μg per day. Moreover, recent epidemiological studies around the world show that iodine intake during pregnancy is insufficient in many countries, even in developed countries like Australia, Spain and Italy. In the present work an overview of the importance of iodine nutrition during pregnancy is given.

Importancia del yodo en la gestación. El yodo es un nutrimento constituyente indispensable de las hormonas tiroideas (HT). Las HT participan activamente en periodos críticos del desarrollo cerebral durante las etapas embrionaria, fetal y posnatal. Por lo tanto la ausencia o deficiencia de las HT o de yodo en estas etapas del desarrollo produce un daño cerebral irreversible. De hecho, se sabe que la deficiencia de yodo es la principal causa de daño cerebral prevenible en el mundo. Debido a los ajustes fisiológicos propios de la gestación los requerimientos de yodo se incrementan notablemente, pasando de 150 μg al día en la mujer adulta no gestante a 250 μg al día durante el embarazo. Por otra parte, estudios epidemiológicos recientes hechos en todo el mundo muestran que el consumo de yodo durante la gestación es insuficiente en varios países; incluso en países desarrollados como Australia y España e Italia. En la presente revisión se da un panorama general de la importancia del consumo adecuado de yodo durante la gestación.

Importance of iodine in pregnancy.

Iodine is an essential constituent of thyroid hormones (TH). TH actively take part in critical periods of brain development during embryonic, fetal and postnatal stages. Therefore the absence of TH or iodine in these critical periods produces an irreversible brain damage. In fact, it is known that iodine deficiency is the leading cause of preventable brain damage worldwide. Because of the physiological adjustments during pregnancy iodine requirements increase significantly from 150 microg per day in non-pregnant adult women to 250 microg per day. Moreover, recent epidemiological studies around the world show that iodine intake during pregnancy is insufficient in many countries, even in developed countries like Australia, Spain and Italy. In the present work an overview of the importance of iodine nutrition during pregnancy is given.

Iodine nutrition status in pregnant women in Mexico.

BACKGROUND: Iodine nutrition during pregnancy has become an important public health concern because of the deleterious impact of iodine deficiency on brain development during fetal and early postnatal life. Iodine nutrition status can be assessed in a population by the median urinary iodine concentration (UIC). World Health Organization, the United Nations Children's Fund, and the International Council for Iodine Deficiency Disorders have established that a median of UIC between 150 and 249 µg/L in pregnant women indicates an adequate iodine intake. The aim of this study was to assess iodine nutrition status in Mexican pregnant women. METHODS: Two hundred ninety-four pregnant women receiving prenatal care in the Public Medical Units of the State Ministry of Health for each pregnancy trimester (first, n=60; second, n=103; and third, n=131) in Queretaro, Mexico, were enrolled to assess UIC by the Sandell-Kholtoff method. RESULTS: The median of UIC was 273, 285, and 231 µg/L in the first, second, and third trimesters of gestation, respectively. Globally, the median (range) of UIC was 260 (5-1320) µg/L, and the percentage of samples with UIC below 150 µg/L was 28%. There was no significant difference between the UIC of women using iodine-containing multivitamins compared with those who reported the consumption of noniodized multivitamins (p>0.05). In addition, we found no difference between the UIC of women using iodized table salt compared with those who employed noniodized table salt, with those who did not know whether their table salt was iodized (p>0.05). CONCLUSIONS: Based on the median UIC, iodine intake in Queretaro, Mexico, is slightly above requirements during the first two trimesters, and adequate in the third trimester. The wide Mexican universal iodized salt program seems to supply adequate dietary iodine to pregnant women without health insurance in this region. However, regular monitoring of iodine status is recommended during pregnancy throughout Mexico.

[Bioactivity of thyroid hormones. Clinical significance of membrane transporters, deiodinases and nuclear receptors]. / Bioactividad de las hormonas tiroideas. Importancia clínica de los transportadores de membrana, de las desyodasas y de los receptores nucleares.

The study of the different factors regulating the bioactivity of thyroid hormones is of utmost relevance for an adequate understanding of the glandular pathophysiology. These factors must be considered by the clinician in order to achieve a successful diagnosis and treatment of glandular diseases. Among the factors regulating bioactivity of thyroid hormones are the following: A) Plasmatic membrane hormone transporters, which tissue-specific expression is responsible for the cellular uptake of hormones, B) A set of deiodinating enzymes which activate or inactivate intracellular thyroid hormone, and C) Nuclear receptors which are responsible for the different cellular responses at the transcriptional level. This review compiles analysis and discusses the most recent findings regarding the regulation of thyroid hormone bioactivity, as well as the clinical relevance of different polymorphisms and mutations currently described for membrane transporters and deiodinases. In addition, the main issues and present and future study areas are identified.

Inhibition of intrathyroidal dehalogenation by iodide.

Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.

Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance.

OBJECTIVE: We measured plasma markers of endothelial dysfunction, vascular inflammation, and pro-coagulation in obese Hispanic/Latino children and adolescents with normal glucose tolerance and determined their relationship to body composition and indexes of glucose and lipid metabolism. RESEARCH DESIGN AND METHODS: A total of 38 lean or obese Hispanic children and adolescents (10-18 years of age) were selected. The overweight group (n = 21) had a BMI >85th percentile for their age and sex, and the lean group (n = 17) had a BMI between the 25th and 50th percentiles. Studies included an oral glucose tolerance test, measurements of plasma glucose and lipids, several markers of endothelial function and inflammation, and determination of body composition by dual X-ray absorptiometry. RESULTS: The obese group had higher systolic blood pressure and plasma triglycerides and was more insulin resistant than the lean group. The obese group also had higher plasma soluble intercellular adhesion molecule (259.5 +/- 60.0 vs. 223.2 +/- 47.5 ng/ml, P = 0.047), tumor necrosis factor-alpha (2.57 +/- 1.1 vs. 1.74 +/- 0.6 pg/ml, P = 0.008), high-sensitivity C-reactive protein (2.0 vs. 0.13 mg/l, P < 0.0001), plasminogen-activated inhibitor-1 (47.0 +/- 35.7 vs. 12.0 +/- 5.2 ng/ml, P < 0.0001), tissue plasminogen activator (6.1 +/- 1.9 vs. 4.1 +/- 0.8 ng/ml, P = 0.001), and white blood cell count (6.9 vs. 5.3 x 10(3), P = 0.031) and lower levels of adiponectin (8.7 +/- 3.3 vs. 12.6 +/- 5.2 microg/ml, P = 0.022). No significant differences were observed for soluble vascular cell adhesion molecule or interleukin-6. CONCLUSIONS: Overweight Hispanic children and adolescents with normal glucose tolerance exhibit increased plasma markers of endothelial dysfunction and subclinical inflammation in association with obesity and insulin resistance. These abnormalities may predispose them to the development of type 2 diabetes and cardiovascular disease.

Analysis of fasting plasma glucose values for optimal detection of abnormal responses on the oral glucose tolerance test in at-risk study subjects.

OBJECTIVE: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for having type 2 diabetes. METHODS: All patients who underwent a 2-hour OGTT during an 18-month period were included in this study. Pretest and posttest odds, likelihood ratios, and receiver operating characteristic curves were used to identify the FPG value most strongly associated with an abnormal result on the OGTT (either diabetes or impaired glucose tolerance [IGT]). RESULTS: Of the 1,371 patients who underwent an OGTT during the designated study period, 1,239 fulfilled the inclusion criteria. The prevalence of IGT was 25.34% (314 patients). Diabetes was diagnosed in 141 patients (11.38%). IGT was more commonly found in the FPG strata below 115 mg/dL; above this value, diabetes was more frequently diagnosed. In general, the percentage of cases of IGT increased progressively throughout the "normal" FPG range. The prevalence varied from 11.4% (in patients with FPG values <80 mg/dL) to 32% (in those with FPG levels from 95 to 99.9 mg/dL). FPG values between 95 and 99.9 mg/dL had a likelihood ratio of 2.1 for detecting an abnormal OGTT response, of 1.8 for detecting diabetes, and of 1.66 for detecting IGT. The odds ratio for detecting either IGT or diabetes was increased 2-fold by performing an OGTT. The FPG threshold with the best ability for detecting an abnormal response on the OGTT was 95 mg/dL (sensitivity of 0.72 and specificity of 0.65). CONCLUSION: In patients at risk for type 2 diabetes, the FPG cut point (95 mg/dL) most useful for detecting an abnormal OGTT response is included in the normal range of the FPG.

Genetic heterogeneity of autosomal dominant hypercholesterolemia in Mexico.

BACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apoB) genes, respectively. A third locus on chromosome 1p34.1-p32 was recently linked to FH and the responsible gene has been identified [protein convertase subtilisin/kexin type 9 (PCSK9)]. METHODS: We assessed the contribution of the LDLR, apoB, and PCSK9 genes as cause of FH in Mexico. Forty six unrelated probands, as well as 68 affected and 60 healthy relatives, were included. RESULTS: All index cases were diagnosed as having heterozygous autosomal dominant FH. Seventeen of the 46 index cases had LDLR gene mutations, four of which were novel (Fs92ter108, C268R, Q718X, and Fs736ter743); and only one patient had an apoB mutation (R3500Q). We sequenced the PCSK9 gene in the remainder of the 28 probands with no identified LDLR or APOB gene defects; however, no PCSK9 mutations were found, including one large kindred with positive linkage to the 1p34.1-32 locus (multipoint LOD score of 3.3) and two small pedigrees. Linkage was excluded from these three loci in at least four kindreds suggesting that other yet uncharacterized genes are involved. CONCLUSIONS: Our results underline substantial genetic heterogeneity for FH in the Mexican population.

A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.

Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of beta-strands beta6 and beta7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.

Familial hypercholesterolemia due to ligand-defective apolipoprotein B100: first case report in a Mexican family.

BACKGROUND: Familial defective apolipoprotein B100 (FDB) is one of the known causes of familial hypercholesterolemia (FH). Its frequency among subjects with FH varies among ethnic groups; information on FH is insufficient for populations from Latin America. We proposed to describe prevalence of FDB in a cohort of Mexican FH probands (n = 30). METHODS: We searched for the known FDB mutations using polymerase chain reaction assays. In this set of patients, mean lipid values were representative of FH (cholesterol 351 mg/dL, LDL cholesterol 274 mg/dL, HDL cholesterol 51 mg/dL, and triglycerides 132 mg/dL). RESULTS: One subject with Arg3500Gln mutation was found: a 44-year-old male with a history of coronary heart disease (CHD) among paternal relatives. His lipid profile was cholesterol 370 mg/dL, LDL-cholesterol 300 mg/dL, HDL-cholesterol 32 mg/dL, and triglycerides 189 mg/dL. Tendinous xanthomata were detected. Three of four siblings, one of three sons, and one of nine nieces and nephews carried the mutation. The mutation was confirmed by automated sequencing. Tendinous xanthomata were absent in affected subjects younger than age 20 years; additionally, the subjects had borderline cholesterol levels. CONCLUSIONS: Our data suggest that FDB explains the small number of FH cases in Mexico. Inclusion of molecular biology assays to the clinical laboratory makes it possible to diagnose affected individuals with borderline cholesterol levels or without tendinous xanthomata.