ABSTRACT
The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.
Subject(s)
Autistic Disorder/genetics , Carrier Proteins/genetics , Chromosomes, Human, Pair 2 , Cyclic AMP/metabolism , Guanine Nucleotide Exchange Factors/genetics , Animals , Carrier Proteins/metabolism , Female , Genetic Predisposition to Disease , Genetic Testing , Genetic Variation , Genotype , Guanine Nucleotide Exchange Factors/metabolism , Humans , Linkage Disequilibrium , Male , Mice , Mutation, Missense , Pedigree , Polymorphism, Single NucleotideABSTRACT
The VNTR 3'APOB and D1S80 loci were studied in a sample of 179 individuals living in the Recanati Area (Central Italy). For 3'APOB, we found 34 genotypes and 11 alleles. The system was in Hardy-Weinberg equilibrium. The observed and expected heterozygosity were 0.788 and 0.798 respectively. The discrimination power was 0.96, the a-priori paternity exclusion power was 0.619 and the polymorphism information content was 0.773. For D1S80, we found 45 genotypes and 18 alleles. The system deviated significantly from Hardy-Weinberg equilibrium. The observed and expected heterozygosity were 0.696 and 0.790 respectively. The discrimination power was 0.96, the a-priori paternity exclusion power was 0.617 and PIC was 0.767. The Recanati sample was compared with the general Italian frequencies for the 3'APOB locus. A difference of borderline significance was detected (P = 0.04). For D1S80, the sample was compared with a sample from Southern Italy and no significant difference was detected.
Subject(s)
Apolipoproteins B/genetics , Genetics, Population , HLA-D Antigens/genetics , Alleles , Female , Forensic Medicine , Genotype , Humans , Italy , MaleABSTRACT
Hypertension in the elderly represents a cardiovascular risk factor which increases due to ageing and to the raise of blood pressure (BP) values. The occurrence of hypertension depends on an interaction between genes and environment. An available antihypertensive therapy causes a reduction in the incidence of cardiovascular events. An antihypertensive therapy in the elderly must take into account: in these subjects BP might be spontaneously lower over 30 mmHg in 24 hours; people normally have a postprandial BP reduction; sudden raises or falls of pressure cause cerebral hypoperfusion; some adverse vents of hypertensive drugs worsen their quality of life, not reducing myocardial hypertrophy; possible electrolytic troubles might worsen a congestive heart failure; drastic diets cause a raise in the incidence of colorectal tumours; a high heart rate increases the risk of sudden death; a chronic NSAID intake might cause or aggravate a hypertensive state; a reduction of natrium chlorure and lipides in the diet might cause a BP fall. In short, the BP reduction should be gradual in the hypertensive elderly in order to avoid the occurrence of cardiovascular events, diets should be balanced, rich in fibres and vitamins to avoid colorectal tumours. Besides, NSAID must be used by these patients for a short time and all therapeutic interventions should improve their quality of life.
