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Biomedical subjects

M H Hutz

Publications and source records attributed to M H Hutz.

At least 19 recordsLinked to original sources
PubMed2006

The GNB3 C825T polymorphism and depression among subjects with alcohol dependence.

The T allele of the C825T polymorphism in the G-protein beta(3) subunit gene (GNB3) is related to the increase of signal transduction by the G-protein. G-proteins are intermediary paths in signal transduction from receptors involved in mood regulation and substance dependence. We studied the C825T polymorphism in individuals with (i) alcohol and nicotine dependence (n = 109), (ii) nicotine dependence only (n = 117) and (iii) non-dependent controls (n = 108). We also tested for possible associations with psychiatric comorbidities among alcohol-dependent individuals. No differences were detected for allele and genotype frequencies in individuals with or without dependencies. Alcohol-dependent individuals with the heterozygous genotype presented more frequently major depressive disorder (chi(2) = 12.34; p = 0.002). These findings, taken together with other studies suggesting an influence of the C825T polymorphism in major depressive disorder, support the hypothesis of the involvement of G-proteins in mood regulation.

Alcoholism↗
PubMed2006

Estrogen receptor 1 gene polymorphisms and coronary artery disease in the Brazilian population.

We examined the association of three established single nucleotide polymorphisms, IVS1-397T>C, IVS1-351A>G, and +261G>C, in the ESR1 gene with the prevalence and severity of coronary atherosclerosis in a southern Brazilian population of European ancestry. Three hundred and forty-one subjects (127 women and 214 men) with coronary artery disease (CAD) were classified as having significant disease (CAD+ patient group) when they showed 60% or more luminal stenosis in at least one coronary artery or major branch segment at angiography; patients with 10% or less luminal stenosis were considered to have minimal CAD (CAD- patient group). The control sample consisted of 142 subjects (79 women and 63 men) without significant disease, in whom coronary angiography to rule out the presence of asymptomatic CAD was not performed. The polymorphisms were investigated by polymerase chain reaction followed by restriction analyses. In the male sample, the +261G>C*C allele was more frequent in CAD+ than CAD- subjects (8 versus 1%, P = 0.024). Homozygosity for the C allele of the IVS1-397T>C polymorphism was also significantly associated with increased CAD severity (OR: 2.99; 95% CI = 1.35-6.63; P = 0.007). In agreement with previous findings, these results suggest that the IVS1-397T>C*C allele was associated with CAD severity independent of gender, whereas the association of the +261G>C variant with CAD was observed in males only. The relation between ESR1 variation and CAD may influence clinical decisions such as the use of hormone therapy, and additionally will be helpful to identify the genetic susceptibility determinants of cardiovascular disease development.

Brazil↗
PubMed2006

Application of an African Ancestry Index as a genomic control approach in a Brazilian population.

Ten ancestry informative markers were investigated in 101 coronary artery disease patients and 102 healthy controls from a Southern Brazilian population, in order to determine if stratification occurs in this population. The degree of African admixture detected in this population was estimated to be as high as 6%, but no differences between cases and controls were observed. Using an African Ancestry Index (AAI) that estimates admixture at the individual level it was possible to remove from the samples those individuals with evidence of African admixture. Therefore we have shown that it is possible to control for population stratification by choosing individuals, without the loss of statistical power that occurs with the use of other methods of genomic control.

Africa↗
PubMed2005

APOA1/C3/A4 gene cluster variability and lipid levels in Brazilian children.

Genetic studies have suggested that polymorphisms of genes coding for apolipoproteins are significant determinants of serum lipoprotein and lipid levels in adults. However, only a few studies have investigated the association of these polymorphisms in children. Therefore, in the present investigation we studied the distribution of APOA1 -75 G>A, +83 C>T, APOC3 -482 C>T, -455 T>C and 3238 C>G, and APOA4 Q360H and T347S polymorphisms and their influence on plasma lipoprotein levels in children from a Brazilian northeastern admixed population. The seven polymorphic sites were genotyped in 414 children aged 5 to 15 years (mean 8.9 +/- 2.9). The genotypes of the seven polymorphic sites were assessed by PCR-RFLP methods. The frequencies of the less common alleles were, in general, intermediate among parental populations, as expected. Strong linkage disequilibrium was detected between polymorphisms at the APOA1, APOC3 and APOA4 loci in this admixed population sample. Overall the genotype effects seen in adults were weaker or absent in children. The APOC3/-455 and APOA4 T347S variants showed significant effects on HDL cholesterol in girls (P = 0.033 and P = 0.016, respectively). Significantly higher plasma total (P = 0.003) and LDL cholesterol (P = 0.004) levels were observed in boys who were carriers of the 3238G allele at the APOC3/3238 C>G site. These results disclosed an overall absence of associations between these polymorphisms and lipids in children. This finding is not unexpected because expression of the effect of these polymorphisms might depend on the interaction with environmental variables both internal and external to the individual.

Adolescent↗
PubMed2005

The DBH -1021 C/T polymorphism is not associated with alcoholism but possibly with patients' exposure to life events.

Two DBH polymorphisms were investigated in 114 Brazilian alcoholics of European descent and 233 controls. Personality and life events were also analyzed among alcoholics. No significant differences were observed in allele or genotype frequencies between alcoholics and controls. No association was detected between the polymorphisms and personality dimensions. Carriers of the -1021 T allele presented a higher number (F = 7.49; P = 0.007) of life events. This study provides a preliminary indication that the DBH -1021 C/T polymorphism influences the exposure to life events.

Alcoholism↗
PubMed2005

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status.

Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G>A and 1730A>G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n=187; mean age=34+/-9.7 years), postmenopausal women exposed to hormone replacement therapy (HRT) (n=118; 56+/-6.7 years) and postmenopausal women unexposed to HRT (n=167; 58+/-9.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P=0.027 and 0.001, respectively) and T-chol levels (P=0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G>A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources.

Adult↗
PubMed2005

Estrogen-metabolizing gene polymorphisms and lipid levels in women with different hormonal status.

Endogenous and exogenous sex steroid hormones have multiple effects on lipid and lipoprotein metabolism. It is also known that estrogen has antiatherogenic actions, therefore we considered examining whether there was any association between polymorphisms in estrogen-metabolizing genes and lipid levels in women. We investigated the association between variants in genes related to estrogen biosynthesis (CYP19-TTTA(n)) and estrogen catabolism (CYP1A1*2A, CYP1A1*2C, CYP1A2-Asn516Asn, CYP3A4*1B, and COMT-Val158Met) with serum lipid levels in a cross-sectional study with 472 Brazilian women of European descent. They were divided into three subgroups according to their hormonal status: premenopausal women (n=187), postmenopausal women exposed to hormonal replacement therapy (HRT) (n=118), and postmenopausal women unexposed to HRT (n=167). The postmenopausal women receiving HRT who were carriers of the CYP3A4*1B variant showed lower low-density lipoprotein cholesterol levels than wild-type homozygotes. Premenopausal women homozygous for the CYP1A1*2C allele had higher high-density lipoprotein cholesterol levels than heterozygotes. While the CYP1A1*2C variant probably has a higher catalytic activity, the functional implications of the CYP3A4 polymorphism are still uncertain. These data are the first attempt to associate estrogen metabolism genes to lipid levels in women.

Adolescent↗
PubMed2005

Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes.

We investigated the effect of single-nucleotide polymorphisms in sterol regulatory element-binding factors-1a and -2 (SREBF-1a and SREBF-2) and SREBF cleavage-activating protein (SCAP) genes on lipid-lowering response to simvastatin. In all, 146 hypercholesterolemic patients of European descent were prospectively treated with simvastatin 20 mg/day for over 6 months. Of these 99 subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. The mean percentage decrease in plasma total cholesterol (TC) was greater in subject carriers of SCAP 2386G allele compared with those homozygous for 2386A allele (-29.6+/-13.4 vs -22.1+/-13.8%, P=0.007). About 61% of the 2386G carriers were above-average responders for TC levels (DeltaTC -27.8%), whereas only 29% of 2386A homozygous reached this reduction (P=0.009). Our data suggest that the SCAP 2386A>G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment.

Adult↗
PubMed2004

Association between -250G/A polymorphism of the hepatic lipase gene promoter and coronary artery disease and HDL-C levels in a Southern Brazilian population.

Hepatic lipase (HL) is a glycoprotein that plays a major role in remodeling high-density lipoprotein (HDL). The effect of the -250G/A promoter polymorphism on coronary artery disease (CAD) and lipid levels was studied in 231 male CAD patients and in a population-based sample of men and women (n = 514). A sample of 140 men was chosen among those included in the population-based sample as controls for the CAD sample. In the total group of CAD patients, the frequency of the -250A allele was somewhat lower (25% in CAD patients and 32% in controls; p = 0.06), but when the control samples were compared only with the CAD(+) sample (more than 60% of luminal stenosis in at least one coronary artery or major branch segment) the -250A allele was significantly less frequent (23% in the patients vs 32% in controls; p = 0.02). A multiple logistic regression analysis showed that this association was independent of classical CAD risk factors [odds ratio (OR) = 1.79, p = 0.025]. Using multiple linear regression analyses, it has been shown that this polymorphism was a significant factor affecting HDL-C levels in men from the population-based sample (p = 0.001), an interaction between -250G/A variant and wine consumption was also detected (p = 0.001). Thus, our results show that the -250G/A polymorphism in the HL gene is associated with significant variations in HDL-C levels and CAD risk in males.

Adult↗
PubMed2004

Intra- and intercontinental molecular variability of an Alu insertion in the 3' untranslated region of the LDLR gene.

One-hundred three individuals from two Mongolian, two Siberian, and ten native American populations were studied in relation to a 340-bp sequence from an Alu insertion located in the 3' untranslated region of the LDLR gene. Seven haplotypes have been determined, and haplotype B1 was the most common, accounting for about half the sequences found. In general, diversity values are quite high, about 2.5 times higher than those found in other autosomal Alu sequences. Almost all (93%) of the variability occurs at the intrapopulation level, but the greatest among-group differentiation (6-8%) was found when we grouped in a single population all Native Americans plus Siberian Eskimos and Chukchi and compared them with Mongolians. This result is compatible with earlier mtDNA and Y-chromosome suggestions of a single origin for the first colonizers of the American continent. With this nuclear locus it was not possible to broadly distinguish between Central and South American natives. No evidence of selection or marked demographic changes was obtained with these data.

3' Untranslated Regions↗
PubMed2003

Interaction between SREBP-1a and APOB polymorphisms influences total and low-density lipoprotein cholesterol levels in patients with coronary artery disease.

In this study, we examined the insertion/deletion (Ins/Del) and XbaI polymorphisms of the apolipoprotein B (APOB) gene and the -36delG polymorphism in the sterol regulatory element binding protein-1a (SREBP-1a) gene in 298 patients with non-diabetic angiographically assessed coronary artery disease (CAD), and 188 healthy controls, from a Brazilian population of European descent. Del/X+ haplotype carriers had higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in patients (TC, p = 0.05; LDL-C, p = 0.049) and controls (TC, p = 0.004; LDL-C, p = 0.013). No association was detected between the SREBP-1a-36delG polymorphism and lipid levels, but a significant interaction effect between APOB and SREBP-1a polymorphisms was observed in the patient sample on TC (p = 0.005) and on LDL-C (p = 0.019) levels. Carriers of the APOB Del/X+ haplotype and SREBP-1a G-G- genotype showed the highest levels of these lipid parameters. This effect of interaction was not observed in the control sample. Despite the associations with lipids, these polymorphisms were not associated with CAD risk or severity in this sample.

Adult↗
PubMed2003

Further evidence for the association between obesity-related traits and the apolipoprotein A-IV gene.

OBJECTIVE: To investigate associations and gene-environment interactions of APOA-IV gene polymorphisms with obesity-related phenotypes in a Brazilian population. METHODS: A total of 391 individuals (171 men and 220 women) were genotyped for Xbal, Thr347Ser and Gln360His polymorphisms by PCR-RFLP methods. Adjusted body mass index (BMI) and waist circumference (WC) were compared among genotypes/haplotypes by unpaired t-test or analysis of variance. Gene-environment interactions were tested by analysis of variance using a general linear model. RESULTS: Analysis of the APOA-IV gene variants separately showed that X*2 and 347Ser alleles were associated with higher BMI (P=0.02 for both polymorphisms). Haplotype analysis confirmed this association. For these polymorphisms, the effect on BMI appeared to depend on smoking status (test for interaction, P=0.007 and 0.02, respectively), the Thr347Ser variant was associated with a BMI increase in smokers only (P=0.002). At the single-locus level no association was observed between 360His allele and BMI; however, haplotype analyses showed an association of this gene variant and higher BMI. A trend for association with WC (P=0.05) was observed in male carriers of the 360His allele. The effect of this polymorphism also depended on smoking status (test for interaction, P=0.018). Nonsmoker male carriers of the 360His allele had a larger waist circumference than homozygotes for the Gln allele (P=0.003). CONCLUSION: Our data suggest that the APOA-IV gene polymorphisms investigated are associated with obesity-related traits. The effects of X*2 and 347Ser variants on BMI and the 360His variant on waist circumference depended on smoking status.

Alleles↗
PubMed2003

HLA class II diversity in seven Amerindian populations. Clues about the origins of the Aché.

The study of the HLA variability of Native American populations revealed several alleles specific to one or more of the Latin American indigenous populations. The analysis of Amerindian groups distributed all over the continent might inform about the area of origin and the dispersal of these alleles and shed light on the evolution of this remarkable polymorphism. Moreover, HLA alleles and haplotypes are excellent markers to understand the genetic relationships between populations. For these reasons, we characterized the HLA class II polymorphism in seven South American Amerindian populations and compared the results with those previously reported for other Amerindian groups. The Guarani-Kaiowá (n = 160) and Guarani-Nandeva (n = 87) were from the Brazilian state of Mato Grosso do Sul, the Guarani-M'byá (n = 93) and Kaingang (n = 235) from Paraná state, the Aché (n = 89) from eastern Paraguay, the Quechua (n = 44) from Andean Peru. From Amazonia, a heterogeneous group was analyzed (n = 45). The most frequent alleles and haplotypes are common also in other Amerindian populations. Each HLA-DRB1 allele was typically found in combination with just one DQA1-DQB1 haplotype, most likely as a result of some form of random genetic drift and reduced gene flow from non-Amerindians. The frequency distribution differed significantly among all populations, although differences were less pronounced between the Guarani subgroups. Marker alleles allowed an estimate of European and sub-Saharan African gene flow into these populations: Quechua 23%, Guarani-Nandeva 14%, Kaingang 7%, Guarani-M'byá 4%, Guarani-Kaiowá, Amazonia, and Aché 0%. Interestingly, the DRB1*1413 allele, previously found only among the Guarani-M'byá (frequency 15%), appeared in the Aché (8%). The relationship of the Aché to other Amerindian populations is unclear, and this finding reveals a link with the Guarani. On the basis of genetic distance and the HLA allele/haplotype set, we propose that the Aché are differentiated Tupi-Guarani group, most closely related to the Guarani-M'byá.

Alleles↗
PubMed2003

Methylenetetrahydrofolate reductase (MTHFR) allele frequencies in Amerindians.

Neural tube defects (NTDs) have been associated with abnormalities of folate metabolism. Methylenetetrahydrofolate reductase (MTHFR) is the regulatory enzyme for the conversion of homocysteine to methionine. The C677T mutation in the MTHFR gene affects folate distribution, and homozygosity for the T allele may be associated with an increased risk of NTDs. A second mutation, an A1298C transversion in this same gene, is also associated with an increased risk for NTDs but only in conjunction with the 677T allele. A low incidence of NTDs has been observed in high-altitude populations; however, these studies did not provide information about the allele distribution of genes involved in folate metabolism. This investigation compares allele frequencies of the C677T and A1298C polymorphisms between Quechua people living at 3200-4200 m in the Peruvian Central Andes and an Aché group living at low altitude. Allele frequencies at both loci were not significantly different between the two populations. The absence of the 677T/677T genotypes and of the 677T/1298C arrangement in both groups may indicate a genetic contribution to reduced risk for NTDs; however, factors other than altitude are likely responsible for the low variant allele frequencies in these populations.

Altitude↗
PubMed2002

High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia.

Homozygous sickle cell disease (SCD) has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1%) of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3%) with the same ethnic background (Afro-Brazilians). Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

Adolescent↗