[show abstract][hide abstract] ABSTRACT: Schizophrenia is a complex disease affecting as much as 1% of the global population, constituting the target of considerable effort to identify disease susceptibility genes. Several lines of evidence point to the catechol-O-methyltransferase (COMT) gene as a schizophrenia susceptibility candidate, not only because it encodes a key dopamine catabolic enzyme but also because it maps to the velocardiofacial syndrome region of chromosome 22q11, which has long been associated with predisposition to the disease. Several case-control and family-based studies have been conducted to examine the possible association of COMT with this disorder; however, these studies have produced conflicting results. To further assess the genetic contribution of COMT variants to schizophrenia susceptibility, three single-nucleotide polymorphisms (rs2075507, rs4680 and rs362204) were investigated in a sample of 74 family trios from the Cuban population. Restriction fragment length polymorphism was used to identify the allelic variants, employing statistical tools based on transmission disequilibrium tests to find possible associations. In this study, the first of its type performed in the Cuban population, we found an association of rs2075507 and rs362204 at allelic levels with a p < 0.05; also finding an association of haplotype 1-2-1 with the disease.
[show abstract][hide abstract] ABSTRACT: Recent studies suggest that celiac disease (CD) is common in many developing countries. Because the disease may be under diagnosed in Cuba, we studied the presence of the disease in a group of apparently healthy adult.
It was to assess for the first time, the presence of silent CD in a cohort of healthy Cuban adults individuals and to evaluate the tools for diagnosis of CD in this group.
A total of 200 healthy Cuban adult from Havana City were evaluated. Tissue transglutaminase antibodies (tTGA) were determined by one-step immunochromatographic assay and by commercial ELISA kit. CD specific human leukocyte antigen (HLA) typing was performed by polymerase chain reaction amplification, using sequence-specific primers. In the subject positive for tTGA, the CD was confirmed by intestinal biopsy.
From the 200 studied individuals, only one subject was identified as positive by both assays, being submitted to duodenal biopsy. Morphological changes consistent with CD were found and also supported by HLA-DQ2 (HLA-DQA1*0501-DQB1*02). In the follow-up after one year, histological recovery was assessed by a second intestinal biopsy and the serological marker became negative.
This study confirms the existence of silent CD among healthy adult in Cuba and highlights the importance of mass screening for this disease among them. The one-step immunochromatographic assay is a good tool for this purpose.
[show abstract][hide abstract] ABSTRACT: The extreme polymorphism found at some of the human leukocyte antigen (HLA) system loci makes it an invaluable tool for population genetic analyses. In the present study the genetic polymorphism of the Cuban population was estimated at HLA-A, -B, and -Cw loci by DNA typing. HLA class I allele and haplotype diversity were determined in 390 unrelated Cuban individuals (188 whites and 202 mulattos) from all over the country. In whites 19, 27, and 14 allele families for the HLA-A, -B, and -Cw loci, respectively, were identified. In mulattos, for the same loci, 20, 18, and 14 allele families were identified. Allele and haplotypes frequencies, comparisons with other worldwide populations based on genetic distances, neighbor-joining dendrograms, and correspondence analyses were estimated. Most of the identified allele groups and haplotypes are also common to sub-Saharan African and Europeans populations. However, Amerindian and Asian alleles were also detected at lower frequencies. The results clearly reveal the high diversity and interethnic admixture of the studied population. Our results provide useful information for the further studies of the Cuban population evolution and disease association in terms of HLA class I genes.
Human Immunology 12/2007; 68(11):918-27. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The angiotensin converting enzyme (ACE) is a key protein of the renin angiotensin system, whose main function is the conversion of angiotensin I to II. ACE is involved in the physiological control of blood pressure and it is a candidate gene for essential hypertension in humans. We tested the relevance of the ACE insertion/deletion (I/D) polymorphism in our population.
We recruited 243 hypertensive and 407 normotensive subjects in the city of Havana, matched according to age, sex and ethnic group. The ACE (I/D) polymorphism was determined by the polymerase chain reaction (PCR) technique. The fit of genotype frequencies to Hardy-Weinberg proportions was evaluated in all groups analyzed. The possible association between the ACE I/D polymorphism and hypertension status was tested by chi2 and odds ratio tests.
All groups but black female cases were in Hardy-Weinberg equilibrium. The frequencies of the D allele in hypertensive/normotensive subjects were 0.61/0.59 in white males, 0.58/0.58 in white females, 0.47/0.59 in black males and 0.58/0.54 in black females. The distribution of ACE genotypes differed significantly between cases and controls only in black women according to the additive model (chi2p=0.04) but the adjusted OR did not show significant association (OR 1.14 95% CI 0.62 to 2.10).
The ACE I/D polymorphism was not associated with hypertension in our multiethnic sample. While the chi2 test for additive model in black women suggested a marginal significance, the adjusted OR did not show any significant association.
[show abstract][hide abstract] ABSTRACT: Celiac disease (CD) susceptibility has been strongly associated with HLA-DQ2 and HLA-DQ8. The main objective of this study was to assess the distribution of HLA DQA1*0501 and DQB1*02 alleles (DQ2) for the first time in a group of Cuban celiac patients. We evaluated 22 patients, 54 first-degree relatives, and 60 controls for detection of antitissue transglutaminase (tTG)-specific antibodies in serum. We found that 100% of the probands and 19% of the first-degree relatives were positive for the antibodies in serum. We did not detect any specific response for the healthy control individuals. We observed a significant over-representation of DQ2 heterodimer, both in patients and relatives. In the group of patients, 86.3% were positive for DQA1*0501, 90.2% were positive for DQB1*02, and 86.3% were positive for both alleles. The frequencies in relatives and controls were as follows: 70%, 90%, and 70%; and 56.6%, 45%, and 20%, respectively. In conclusion, we found that the proportion of our celiac patients carrying DQ2 was similar to the proportion of CD patients reported in populations with different genetic backgrounds. These results underline the primary importance of HLA-DQ alleles in susceptibility to celiac disease.
Human Immunology 09/2006; 67(8):639-42. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The antigenicity of two recombinant NS3 proteins cloned in E. coli was compared by ELISA. The truncated rNS3 recombinant protein encompasses the amino acids from 1234 to 1432 of the Hepatitis C Virus (HCV) polyprotein, and the CIB-c33c protein encloses the entire HCV c33c sequence (aa 1192-1457). Seroconversion sera to NS3 from the Boston Biomedical panel PHV908 were used for evaluation. Our results show that the CIB-c33c protein has a better antigenicity than the rNS3 protein. Antigen CIB-c33c was recognized by the sera at the HCV seroconversion phase exclusively with antibodies against the NS3 region. Comparisons between both proteins suggest that the 25 aa fragment sequence presented at the c33c carboxyl-terminal is important for antibody recognition. The synthetic peptide encompassing this 25 amino acid fragment was not recognized by sera in seroconversion for HCV, suggesting that this fragment requires the presence of the remaining c33c region to expose its antigenicity. The new variant of the c33c protein obtained (CIB-c33c), expressed at high levels in E. coli and highly purified (>90% of purity) by one- step metal affinity chromatography, showed improved antigenic properties. Moreover, it increased the performance of anti-HCV diagnosis, and was able to detect sera in the seroconversion phase, thereby reducing the diagnostic seronegative window.