Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.

Carotenoid availability affects the development of a colour-based mate preference and the sensory bias to which it is genetically linked

Regardless of their origins, mate preferences should, in theory, be shaped by their benefits in a mating context. Here we show that the female preference for carotenoid colouration in guppies (Poecilia reticulata) exhibits a phenotypically plastic response to carotenoid availability, confirming a key prediction of sexual selection theory. Earlier work indicated that this mate preference is genetically linked to, and may be derived from, a sensory bias that occurs in both sexes: attraction to orange objects. The original function of this sensory bias is unknown, but it may help guppies find orange-coloured fruits in the rainforest streams of Trinidad. We show that the sensory bias also exhibits a phenotypically plastic response to carotenoid availability, but only in females. The sex-specificity of this reaction norm argues against the hypothesis that it evolved in a foraging context. We infer instead that the sensory bias has been modified as a correlated effect of selection on the mate preference. These results provide a new type of support for the hypothesis that mate preferences for sexual characters evolve in response to the benefits of mate choice--the alternatives being that such preferences evolve entirely in a non-mating context or in response to the costs of mating.

Lipoprotein-genotype associations in Trinidadian neonates

OBJECTIVES: We hypothesized that common variation in the angiotensinogen (AGT), beta-3-adrenergic receptor. intestinal fatty acid-binding protein, serum paraoxonase, paraoxonase-2, hepatic lipase, apolipoprotein E (APOE), and Werner helicase (WRN) genes would be associated with variation in biochemical phenotypes in a previously unstudied neonatal sample. DESIGN AND METHODS: We examined associations of both nongenetic and genetic variables with plasma lipoprotein traits in neonates from Trinidad. RESULTS: Among nongenetic variables, we found significant associations between plasma concentrations of 1.) lipoprotein (a) [Lp(a)] and both ethnicity (p=0.037) and birth weight (p=0.001); 2)total cholesterol and gender (p=0.010); 3)triglyceride and birth weight (p=0.035); and 4)apolipoprotein A1 and gender (p=0.016). Among genetic variables, we found that: 1)common variation on chromosome 1q in AGT codon 235 was significantly associated with variation in plasma apolipoproteins Al (p<0.0001); and 3)common variation in APOE at codons 112 and 158 was significantly associated with variation in plasma triglycerides (p=0.013). CONCLUSIONS: The associations with AGT and WRN are novel and may have resulted either from direct influence of the genetic variants or through linkage disequilibrium with other functional loci, such as the familial combined hyperlipidemia locus on chromosome 1q in the case of AGT. Despite the fact that there are some limitations in making determinations from cord blood, the results suggest that there may be genetic determinants of plasma lipoproteins in neonates. (AU)

Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry

Variation in the PON1 and PON2 genes has been shown to be associated with coronary heart disease risk in adults of South Asian origin. In this group, low birth weight is also associated with coronary heart disease risk. We therefore hypothesized that variation in PON1 and PON2 genes may be associated with variation in birth weight. This relationship was examined in 90 consecutive Trinidadian neonates of different ethnic origins. We found that variation in PON2 was significantly associated with variation in birth weight in Trinidadian neonates of south Asian origin. Among the neonates of South Asian origin, those who were homozygous for PON A148/A148 had significantly lower birth weight, by approximately 00 g, compared with those with the other two genotypes (P < 0.05). For neonates of south Asian origin, PON2 A148/A148 homozygotes were significantly more prevalent in those comprising the lowest tertile for birth weight than those comprising the highest tertile (0.41 versus 0.24, P < 0.05). There were no significant associations of PON variation with any phenotype in other ethnic groups. We conclude that among neonates of South Asian origin, homozygosity for PON2 A148/A148, is associated with significantly lower birth weight. This suggests that genetic factors in the fetus may be important determinants of neonatal birth weight and possibly of more distal adult phenotypes, such as coronary heart disease.(AU)

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy

Human T cell lymphotropic virus-I (HTLV-I) -associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetrameters loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR beta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.(Au)

Morbid risk of schizophrenia in first-degree relatives of white and African-Caribbean patients with psychosis

The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of white patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 white and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of white and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their white counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their white counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.(AU)

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence

We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphomphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. Purpose: the objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. Methods: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype or the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. Results: The age-standardized NHL incidence rate (mean ñ SE) in Jamaica was 1.9 ñ 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 ñ 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95 percent confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. Conclusions: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphomagenesis. Implications: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lymphomagnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations (AU)

Systemic lupus erythematosus, rheumatoid arthritis and HLA phenotypes in Jamaicans

The HLA phenotypes were investigated in 30 Jamaican patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA) an d forty healthy controls. HLA phenotypes were determined by the microcytotoxicity technique, using commercially prepared typing trays. In this study, the HLA phenotypic associations with SLE (HLA-B14, RR 4.3: HLA-A28, RR 4.3) were not statiscally significant. However, a statistically significant lack of HLA-A9 (p<0.01;CP<0.1) was observed in SLE patients compared to healthy controls. In RA patients, a statistically significant associations was noted with HLA-A2 (RR5.1; CP<0.01). No HLA class 11 associations were noted with SLE. Class 11 associations with RA did not achieve statistical significance but included those previously established in other populations. The preliminary data obtained from this study indicate differences in the patterns of HLA phenotypes in Jamaican patients with SLE and RA compared to those observed in such patients elsewhere. Further studies involving larger groups of patients and typing at the serological, cellular and molecular levels are clearly warranted (AU)

Blood group frequencies of the population of Trinidad and Tobago, West Indies

The results of grouping tests performed on blood samples collected over a five-year period at the Trinidad and Tobago Forensic Science Centre are presented. The samples were tested using the ABO, PGM, EAP and GLO blood group systems. Phenotypic frequencies and allele frequencies for each system were calculated for the two major ethnic groups of the population, the African and East Indian. Matching probabilities, which can be used in the interpretation of physical evidence in forensic cases, were also calculated. (AU)

Immunophenotypic and HLA studies in childhood acute lymphoblastic leukemia in Trinidad, West Indies

Between October 1983 and May 1986, 17 cases of childhood acute lymphoblastic leukemia (ALL) were admitted to the General Hospital, Port of Spain, Trinidad. Fifteen of those cases were under 10 years of age, seven of whom presented with joint or bone pains. Boys outnumbered girls by almost 5:1 and the ethnic distribution showed a preponderance of patients of East Indian origin. At last follow-up (May 1989), the survival rate of the 15 under-ten-year-old patients was 71 percent. Immunophenotype studies on nine of the 17 patients revealed six carrying T cell markers and three carrying markers suggestive of a pre-B phenotype. HLA tissue typing on ten patients showed an enhanced frequency of the HLA-B40 antigen when compared with controls (p less than 0.05). This antigen was present in six of the patients typed and four carried the HLA-A2 and B40 antigens together, two of whom also carried the CW3 antigen and the other two carried untypable C antigens. Three of the four carrying HLA-A2 and B40 have died. Two of the three pre-B cases also carried the HLA-A2 and B40 antigens. HLA studies on three of the four families showed that HLA-A2 and B40 were on the same chromosome, i.e., a haplotype inherited from the mother in each case. None of the cases carried the HLA-B5 antigen although this antigen had a frequency of 37.8 percent in the control group (p less than 0.05 percent). None of the controls with the HLA-B40 antigen carried the CW3 antigen. Further evidence of a disease association must await typing of the D locus antigens but current evidence would suggest an association between HLA-B40 and childhood ALL in Trinidad. (AU)

Genetic variation at the immunoglobulin allotype loci in Creoles of Trinidad

The sera of a sample of 204 Creoles from Trinidad were tested for the presence of polmorphic gene complexes occurring on immunoglobulin light and heavy-chain molecules including the allotypic markers IGKC 1, IGHA2 1 and 2, IGHG1 A, X, F, and Z, and IGHG3 G, G5, B0, B1, B3, B4, B5, C3, C5, S, and T. Nine IGHG (GM) haplotypes occur in polymorphic frequencies (greater than .01) in this population, including known African, Asian, Caucasian, and Amerindian marker haplotypes. Significant differences (P less than .01) were found in the frequency distributions of three IGHI (GM) haplotypes and the frequency of IGKC*1 in these data and data from Creole populations of Belize and St. Vincent. The Creoles of Trinidad and St. Vincent are more similar in IGHG (GM) haplotype distributions than are Trinidad and Belize populations. Previous testing has revealed no significant differences between St. Vincent and Belize Creoles at the Ig allotypic loci. Analysis of migration patterns in the Caribbean suggests that different rates of Asian migration have maintained regional diversity at these loci, while continuous gene flow from the eastern Caribbean to Trinidad has had a relative homogenising effect on the gene pools of this area. (AU)

Comparison of homozygous sickle cell disease in Northern Greece

The clinical and hematological features of homozygous sickle cell (SS) disease were compared in 30 Greek and 310 Jamaican patients. Deletional O-thallassaemia, which modifies SS disease, is rare among Greek patients, so only Jamaican patients with four O-globin genes were included in the control group. Greek patients had higher total haemoglobin concentration and red cell counts, and lower mean cell haemoglobin concentration (MCHC) and reticulocyte counts. They also had a more normal body build and more adults had persistent splenomegaly. Fewer had a history of leg ulceration or priapism but more reported acute chest syndrome. The comparitively mild disease in Greek patients is consistent with less haemolysis and sickling and therefore less bone marrow expansion. In the absence of amelioriating factors such as high HbF concentration or O-thalassaemia, these findings may be explained by the low MCHC. (AU)

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis

Twelve long term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-I) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long term interlukin-2-dependent cell lines exhibited a pattern characteristic of CD4+ -activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50 percent of the cells exhibited HTLV-I antigens by IF. However numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high M-r polypeptides were detected by Western blot in cell lysates when comparing TSP-or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46. (AU)

Variability in rates of alloimmunization in different groups of children with sickle cell diseases: effect of ethnic background

We evaluated the incidence of red blood cell alloimmunization in children with sickle cell disease from different backgrounds using standard blood banking techniques. Transfusion number, sequence of antibody formation, and antigen phenotyping were analysed. Children with non-American ethnic origins had a 42.9 percent incidence of alloimmunization compared to 17.6 percent in American patients. Antigen frequencies were similar in the two groups. Fewer transfusions resulted in more antibodies in the non-American children. We recommend that all sickle cell patients be fully phenotyped prior to initiation of transfusion therapy. Phenotypically matched units do not appear to be indicated for the majority of sickle cell patients receiving either simple or transfusion, but should be considered for patients of non-American ethnic origin once such patients become immunized (AU)

Neonatal screening for sickle cell disease in the Eastern Province of Saudi Arabia

Neonatal screening for sickle cell disease has been established in three hospitals in the Eastern Province of Saudi Arabia. In the first 17 months of this programme, 5630 cord blood samples were screened with the detection of 47 babies with an FS phenotype. The sickle cell trait occurred in 4.4 percent births at Al Khobar, in 6.7 percent in Dammam and in 17.9 percent in Qatif. An apparent excess of the FS phenotype over that predicted from the observed S gene frequency occurred at all three centres. The cause of this excess remains unknown although a high prevalence of sickle cell-beta-o thalassaemia and the effects of non-random mating may be contributory factors. (Summary)

The genetics and molecular basis of alpha thalassaemia in association with Hb S in Jamaican Negroes

We have studied seven Jamaican Negro families in whom the genes for O thalassaemia and the sickle cell mutation (ás) were independently segretated. Using a combination of techniques we identified two O thalassaemia phenotypes which resemble the reserve (O thalassaemia 1) and mild (O thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of O thalassaemia with the genotype in this population. Furthermore, since in each family O thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the OO/OO, -O/-O genotype who are also heterozygous for the ás mutation. Genetic analysis in these families shows that in each case subjects with the O thalassaemia 1 phenotype are homozygous for the O thalassaemia 2 defect (-O/-O). We have found no instances of the genotype --/OO in this population which may explain the rarity of the severe O thalassaemia 2 homozygotes from this population shows that the (-O/) haplotype results from a deletion of one of the linked pair of O globin and that this had probably arisen by an unequal crossover between non-homologous O genes (AU)