Search

The gene encoding adhesion G protein-coupled receptor L3 (ADGRL3, also referred to as latrophilin 3 or LPHN3) has been associated with ADHD susceptibility in independent ADHD samples. We conducted a systematic review and a comprehensive meta-analysis to summarize the associations between the most studied ADGRL3polymorphisms (rs6551665, rs1947274, rs1947275, and rs2345039) and both childhood and adulthood ADHD. Eight association studies (seven published and one unpublished) fulfilled criteria for inclusion in our meta-analysis. We also incorporated GWAS data for ADGRL3. In order to avoid overlapping samples, we started with summary statistics from GWAS samples and then added data from gene association studies. The results of our meta-analysis suggest an effect of ADGRL3variants on ADHD susceptibility in children (n= 8724/14,644 cases/controls and 1893 families): rs6551665 A allele (Zscore = −2.701; p= 0.0069); rs1947274 A allele (Zscore = −2.033; p= 0.0421); rs1947275 T allele (Zscore = 2.339; p= 0.0978); and rs2345039 C allele (Zscore = 3.806; p= 0.0026). Heterogeneity was found in analyses for three SNPs (rs6551665, rs1947274, and rs2345039). In adults, results were not significant (n= 6532 cases/15,874 controls): rs6551665 A allele (Zscore = 2.005; p= 0.0450); rs1947274 A allele (Zscore = 2.179; p= 0.0293); rs1947275 T allele (Zscore = −0.822; p= 0.4109); and rs2345039 C allele (Zscore = −1.544; p= 0.1226). Heterogeneity was found just for rs6551665. In addition, funnel plots did not suggest publication biases. Consistent with ADGRL3’s role in early neurodevelopment, our findings suggest that the gene is predominantly associated with childhood ADHD.

Levodopa is the most used drug to treat motor symptoms in Parkinson’s disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated. DRD2 rs1799732 and DRD3 rs6280 polymorphisms were genotyped by PCR-based methods. Multiple Poisson regression method with robust variance estimators was performed to assess the association between polymorphisms and gastrointestinal symptoms. The analyses showed that DRD2 Ins/Ins (prevalence ratio (PR)=2.374, 95% confidence interval (CI): 1.105–5.100; P=0.027) and DRD3 Ser/Ser genotypes (PR=1.677, 95% CI 1.077–2.611; P=0.022) were independent and predictors of gastrointestinal symptoms associated with levodopa therapy. Despite all the efforts to alleviate GI symptoms, this adverse effect still occurs in PD patients. Pharmacogenetic studies of GI symptoms induced by levodopa therapy have the potential to display new ways to better understand the molecular mechanisms involved in these side effects.

Lipid-lowering therapy has shown a high degree of variability in clinical response and there is evidence that the variability in drug response between individuals is due to genetic factors. Thirteen single nucleotide polymorphisms (SNPs) within the ESR1gene were evaluated with basal lipid and lipoprotein levels, as well as response to lipid-lowering therapy, in 495 hypercholesterolemic individuals of European descent receiving simvastatin or atorvastatin. Significant associations were detected between rs4870061 (P=0.040, corrected P-value (PC)=0.440), rs1801132 (P=0.002, PC=0.022) and the SNP rs3020314 (P=0.013, PC=0.143) with triglyceride (TG) baseline levels. The rs4870061 was also associated with high-density lipoprotein cholesterol (HDL-C) baseline levels (P=0.045, PC=0.495). Regarding statin efficacy, rs2234693 C/C was associated with greater HDL-C increase (P=0.037; PC=0.407) and rs3798577 T allele was associated with greater total cholesterol (TC) reduction (P=0.019; PC=0.209) and greater TG reduction (P=0.026; PC=0.286). These associations suggest that ESR1polymorphisms are in part responsible for the TC, HDL-C and TG variation levels and this effect may be sex-specific.

The presence of the seven-repeat allele of the VNTR in the exon 3 of the dopamine D4 receptor gene (DRD4) has been associated in healthy subjects to the personality trait of novelty seeking. The present study focuses these observations on a sample of Brazilian male alcoholics, evaluated on the temperament dimensions originally described by Cloninger. The genotypes observed are in agreement with those expected under Hardy-Weinberg equilibrium. Subjects with the seven-repeat allele manifest lower harm avoidance scores. No significant differences between subjects with or without the seven-repeat allele in the scores of novelty seeking or reward dependence were observed. The lack of association between novelty seeking and the DRD4 exon 3 polymorphism is further corroborated by the fact that the comorbid antisocial personality disorder is not associated to the presence of the seven-repeat allele. These results could be explained by a biological connection between the personality dimensions of novelty seeking and harm avoidance. © 1999 Lippincott Williams & Wilkins.

A total of 732 individuals affiliated with six Amazonian Indian populations were variously studied in relation to 26 protein genetic systems. Eleven of them were found to be monomorphic in these groups, in accordance with previous investigations. Similarities and dissimilarities (the latter involving the Rh, Duffy, haptoglobin and transferrin systems) were observed in relation to earlier investigations in four of these populations (Galibi, Palikour, Mundurucu and Tenharim). A dimeric, cathodal variant of albumin was found among two Galibi subjects, and the fairly common occurrence of CP*ACAY among some South American Indian populations was confirmed. The results in the six populations were compared with those from 29 others. When relationships are searched for among tribes of the same linguistic group, the factor that seems to be most influential is geographical localization, an exception being the pattern observed among the Cayapo subgroups. The latter shows genetic differences of the same level of magnitude as those observed among Gespeaking tribes.

We have studied the hypervariable D1S80 locus in 185 individuals from five South American Indian tribes, integrating these results with previous investigations. Three alleles (*18, *24 and *30) were common to all tribes, but their frequencies varied between northern and southern populations. Brazilian tribes have a high frequency of *30 (average 35%) while in Argentinian and Chilean Indian populations this allele is present, on average, in 7% of the chromosomes only. Allele *24, the most common in other ethnic groups, was observed in 10% and 25% of northern and southern Amerindians respectively. Genetic distance and dendrogram analyses placed the Argentinian and Chilean tribes closer to Brazilian Caucasians, suggesting non-Indian admixture among them.

Demographic, medical and genetic information was obtained in a population of Carib-speaking Wai Wai Indians living in northern Brazil. At present mortality is low and fertility moderate, with a low variance in offspring number in completed families. Mobility is high, but about two-thirds of the unions are endogamic. Malaria is the main health problem. Phenotype and allele frequencies were obtained for 27 protein genetic systems. Comparison with six other Carib groups indicates closest affinities with another Amazonian tribe, the Arara. Quantification of the intra- and interpopulation genetic diversity in these seven populations indicate that the variation within groups is only slightly lower than the variation between groups. The level of Carib interpopulation diversity, on the other hand, does not differ significantly from that found in 11 Tupi-speaking populations. In accordance with their history of intermarriage with groups which speak slightly different languages, and consider themselves as distinct, the Wai Wai are clearly more diversified at the intrapopulation level than at least three of the six Carib populations with which they were compared.

Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararaô Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararaô. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararaô and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west.

A total of 505 individuals belonging to four populations of three Brazilian Indian tribes were variously studied in relation to 34 genetic systems, and the results were compared with South American Indian averages and five other Tupi populations. Rare variants (CdE of the Rh system, PGM2 11-1, CpA-CAY1, serum cholinesterase2 C5 + and some Gm combinations) were observed with varying prevalences, and the three tribes showed different degrees of departure (28%–40% of differences of 10% or more in gene frequencies) from South American Indian averages. People from two communities who speak the same language and are labelled as belonging to the same tribe (Asurini) showed a large degree of genetic differentiation. Another of the tribes studied (Urubu-Kaapor) link through genetic distance analyses with two other tribes from the north of the continent, forming a distinct microevolutionary unit. These features emphasize the peculiarities of the genetic variation in populations with a hunter-gatherer, rudimentary agriculture type of economy.

A sample of 417 individuals belonging to three Tupi‐Mondé‐speaking tribes (Gavião, Surui, Zoró) were variously studied in relation to 26 genetic protein systems. Previous investigations performed among the Surui in relation to some of these systems were confirmed. The three groups do not depart markedly from the genetic pattern already established for South American Indians and show low inter‐ethnic admixture. When these results are combined with those from 10 other Tupi tribes, two clear geographic groupings (southeastern and northwestern) can be discerned. Using different methods to evaluate the same genetic distance matrices, different patterns of association between the Tupi‐Mondé populations were obtained. The populations are probably too similar among themselves, blurring finer relationships. Am. J. Hum. Biol. 10:711–722, 1998. © 1998 Wiley‐Liss, Inc.