ABSTRACT
BACKGROUND: Human pigmentation is regulated by several genes acting at different stages of melanin formation. Functional and association studies have elucidated the role of several of these genes in pigmentation phenotypes. Forensic and evolutionary studies can benefit from this knowledge. OBJECTIVES: To evaluate the reliability of the prediction of pigmentation phenotypes using a large database of genetic markers in individuals with known phenotypes; and from this try to predict the pigmentation phenotype of prehistoric Homo specimens and of contemporary individuals whose visible phenotypes are not known. METHODS: We compared predicted and observed phenotypic data through an analysis of 124 single nucleotide polymorphisms in 33 genic and seven intergenic regions of 30 subjects, five of them prehistoric, whose complete nuclear genomes are available in UCSC and PSU UCSC public databases. RESULTS: For the molecular predicted versus observed phenotypes, the percentage of agreement was as follows: freckles: 91; skin: 64; hair: 44; eyes: 36; total: 59; while the molecular predicted versus probable (no visible observation available; inferences based on ethnic population characteristics) it was, respectively, 83, 60, 42, 67, and 63. The difference between two sets is statistically nonsignificant (P = 0.75). CONCLUSION: To our knowledge, this is the first article to examine the effect of a large number of genetics markers for phenotype prediction. The approach could be useful for forensic applications, as well as for the determination of possible phenotypes of extinct prehistoric individuals.
Subject(s)
Eye Color , Hair Color , Neanderthals/physiology , Polymorphism, Single Nucleotide , Skin Pigmentation , Animals , Female , Genetic Markers , Humans , Male , PhenotypeABSTRACT
Adrenergic α2A receptor gene (ADRA2A) is one of the most promising candidate genes for ADHD pharmacogenetics. Thus far, three studies have investigated the association between the ADRA2A -1291 C>G polymorphism and the therapeutic response to methylphenidate (MPH) in children with ADHD, all of them with positive results. The aim of this study is to investigate, for the first time, the association between three ADRA2A polymorphisms (-1291 C>G, -262 G>A, and 1780 C>T) and the response to MPH in adults with ADHD. The sample comprises 165 Brazilians of European descent evaluated in the adult ADHD outpatient clinic of the Hospital de Clínicas de Porto Alegre. The diagnostic procedures followed the DSM-IV criteria. Drug response was assessed by both categorical and dimensional approaches, through the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. We found no evidence of association between the three ADRA2A polymorphisms and the therapeutic response to MPH treatment. Our findings do not support a significant role for the ADRA2A gene in ADHD pharmacogenetics, at least among adult patients.
Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/genetics , Central Nervous System Stimulants/therapeutic use , Methylphenidate/therapeutic use , Polymorphism, Single Nucleotide/genetics , Receptors, Adrenergic, alpha-2/genetics , Adult , Analysis of Variance , Female , Gene Frequency , Genome-Wide Association Study/methods , Genotype , Humans , Logistic Models , Male , Middle Aged , Pharmacogenetics , Young AdultABSTRACT
The inflammatory process has been considered an important mediator for the development of atherosclerosis. Interleukin-1 beta (IL1B) is a precursor of interleukin-6 (IL6) in the acute phase of inflammatory response and their levels are elevated in patients with coronary artery disease. The aim of the present study was to further investigate the association of IL-1B and IL-6 gene polymorphisms and angiographically assessed coronary artery disease (CAD) in African- and Caucasian-Brazilians. This report analyzed the IL-1B-511C>T and IL-6-174G>C polymorphisms in 667 patients (253 African-Brazilians and 414 Caucasian-Brazilians) who underwent coronary angiography. Patients with a coronary obstructive lesion 50% presented a higher frequency of the IL-1B-511CC genotype (30.4%) compared to lesion-free individuals (16.5%, p=0.032) in African- but not in Caucasian-Brazilians. No significant genotype frequency difference was identified for the IL-6-174G>C polymorphism in either ethnic groups. However, after correction for other CAD risk factors using multivariate logistic regression, both the IL-1B-511CC [Odds ratio (OR)=2.3; p=0.019] and the IL-6-174GG (OR=2.0; p=0.028) genotypes were considered independent CAD risk predictors in African-Brazilians. This report shows that the IL-1B-511C>T and IL-6-174G>C polymorphisms were associated with CAD risk in African-Brazilians and no association was detected among Caucasian-Brazilians.
Subject(s)
Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Interleukin-1beta/genetics , Interleukin-6/genetics , Polymorphism, Single Nucleotide/genetics , Black People/genetics , Brazil , Case-Control Studies , Demography , Female , Gene Frequency/genetics , Humans , Logistic Models , Male , Middle Aged , White People/geneticsABSTRACT
BACKGROUND: Paraoxonases (PON) are members of an enzyme family involved in preventing low-density lipoprotein oxidation and therefore protecting against atherosclerotic plaque formation. METHODS: We studied the Met55Leu and Gln192Arg PON1 polymorphisms in 712 patients (437 Caucasian- and 275 African-Brazilians) who underwent coronary angiography. RESULTS: Among Caucasian-Brazilians, the homozygous 55LeuLeu frequency was higher among patients with significant coronary artery disease (CAD, obstructive lesions >/=50%) than among lesion-free controls (51% vs. 30.3%; p=0.022) in females, but not in males. The Gln192Arg PON1 polymorphism was not associated with CAD, although 192GlnGln homozygotes presented lower high-density lipoprotein (HDL)-cholesterol (p=0.035) and higher triglyceride (p=0.012) levels than 192Arg allele carriers among Caucasian-Brazilian males, but not females. No other lipid-genotype association was detected. Multivariate logistic regression corrected for classic CAD risk factors shows that 55LeuLeu PON1 homozygotes were at increased CAD risk (odds ratio OR=2.852; p=0.003) and that this genotype interacted with gender in its association with CAD risk (OR=0.290; p=0.006) among Caucasian-Brazilians. CONCLUSIONS: This report shows that the 55LeuLeu PON1 genotype increases CAD risk among female Caucasian-Brazilians, irrespective of other CAD risk factors. In addition, 192GlnGln PON1 homozygotes show higher triglyceride and lower HDL-cholesterol levels in male Caucasian-Brazilians. No associations were detected among African-Brazilians.
