Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans.

OBJECTIVES: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. METHODS: A cross-sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. RESULTS: Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4-5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0-1 risk allele (24.3%): OR 2.31; P = 0.025. CONCLUSIONS: This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism.

Delayed beneficial effect of acute exercise on red blood cell aggregate strength in patients with sickle cell anemia.

Because of the metabolic changes induced by a physical activity, the hemorheological properties of patients with sickle cell anemia could be further impaired and increase the risks for vaso-occlusive complications. However, few studies suggest that moderate physical activity could be beneficial rather than harmful in patients with sickle cell anemia (SCA). However, the definition of what can be considered as a moderate physical activity in SCA patients is imprecise. The present study tested the effects of a short incremental cycling exercise test conducted until the first ventilatory threshold on different biomarkers. Hematological and hemorheological parameters were compared between 8 patients with SCA and 13 healthy subjects (CONT) before, immediately after the end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no significant hematological or hemorheological alteration induced by the exercise in the two groups. However, the exercise resulted in a delayed improvement of the red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the SCA group which was paralleled to the decrease in the platelet count in this group. The present study suggests that such an exercise might be beneficial for microcirculatory blood flow.

Endurance running trial in tropical environment: a blood rheological study.

PURPOSE: The aim of this study was to clarify whether exercising in a tropical climate induces blood rheology alterations despite ad libitum hydration. METHODS: Hematological, biochemical and hemorheological changes were investigated in young healthy adults (N = 9 men, 20.7 ± 0.8 yrs) after a 10-km race in hot and humid conditions. Subjects' maximal aerobic abilities were tested using a maximal ramp exercise. Blood was sampled at rest (TR), at the end of the race (TEx), and after 24 hours of recovery (T24). Ad libitum hydration was allowed during the race. Blood viscosity (ηb), red blood cell deformability (EI), aggregation (AI) and disaggregation shear rate (γ) were measured. RESULTS: Hematocrit, hemoglobin and plasma concentration of chlorine, sodium and potassium did not change in response to exercise. No functional consequence was observed on RBC deformability since EI remained unchanged. Percentages of echinocytes, schizocytes and stomatocytes remained in the subclinical range at all times. AI, γ and ηb did not present change. CONCLUSION: Running exercise in tropical climate with ad libitum hydration does not alter the main rheological properties of blood.

Red blood cell deformability and aggregation, cell adhesion molecules, oxidative stress and nitric oxide markers after a short term, submaximal, exercise in sickle cell trait carriers.

The present study investigated the hemorheological and endothelial alterations in sickle cell trait (SCT) carriers in response to a submaximal exercise. Eleven SCT carriers and 11 subjects with normal hemoglobin performed submaximal exercise for 15 min. Blood was sampled at rest, at the end of exercise, and at 2 and 24 h of recovery. Hemorheological alterations observed in the SCT group were as follows: 1) lower RBC deformability at high shear stress at all time-points, with no relation to oxidative stress, 2) higher disaggregation threshold at all time-points, suggesting RBC hyper-aggregation, and 3) higher blood viscosity at the end of exercise and during recovery. Exercise had a specific influence on the levels of the soluble cell adhesion molecules P and L-selectin in the SCT carriers, with higher P-selectin levels at all time-points and a greater increase in L-selectin levels during recovery. SCT carriers had slightly decreased nitrite levels at 24h of recovery, which might be clinically insignificant. In conclusion, the hemorheological alterations in association with lower NO production found in the SCT carriers are probably not sufficient to explain the medical complications sometimes reported in SCT carriers after exercise.

Adiponectin multimers and ADIPOQ T45G in coronary artery disease in Caribbean type 2 diabetic subjects of African descent.

Ethnic differences may affect the association of adiponectin (Ad) multimers with coronary artery disease (CAD). We analyzed the associations of total Ad, Ad multimers, and T45G polymorphism of ADIPOQ gene with pre-existing CAD. We carried out a cross-sectional study of 216 Afro-Caribbean type 2 diabetic (T2D) subjects. Levels of total Ad, high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) isoforms were measured. Subjects were genotyped. Of the subjects studied, 57 had pre-existing CAD, 77% of whom have had myocardial infarction. Subjects with CAD had lower Ad levels (total and multimers) and a higher frequency carried the minor allele 45G, GG/TG, (18% vs. 8%, P = 0.03) than subjects without CAD. In logistic regression analysis, the models used evaluate Ad in the context of adjustment for metabolic syndrome characteristics. The adjusted odds ratio (OR) of CAD was increased significantly (by factors of 1.05-3.27) for males, older subjects, low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), and carriers of the 45 G allele. For Ad, in model 1 (including only total Ad) the adjusted OR was 2.30; P = 0.03 and, in model 2 (including the three multimers, but not total Ad), the adjusted ORs were 0.73; P = 0.52 (HMW), 2.90; P = 0.01 (MMW), and 2.08; P = 0.09 (LMW). The T45G polymorphism in the ADIPOQ gene and hypoadiponectinemia were associated with CAD in our T2D subjects of predominantly African background. This effect of Ad level was mainly related to the MMW Ad form.

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease.

BACKGROUND: Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. DESIGN AND METHODS: We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). RESULTS: Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. CONCLUSIONS: The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.

Sampling time after tourniquet removal affects erythrocyte deformability and aggregation measurements.

Venipuncture procedures are widely thought to influence biochemical, hematological or hemorheological measurements. In line with the preparation of the new Guidelines for the standardization of hemorheological measurement, we compared various blood rheological parameters (i.e., red blood cell deformability and aggregation indices) assessed in blood samples obtained after 5, 30, 60 and 90 s following the tourniquet removal and a blood sample obtained without applying a tourniquet (control sample). A slight but significant improvement in red blood cell (RBC) deformability after the removal of tourniquet compared to the control sample was observed. RBC deformability was maximal in the samples obtained 30 s after tourniquet removal and remained slightly higher than the control in the following samples (at 60 and 90 s after tourniquet removal). The aggregation index (AI) decreased with time after tourniquet removal reaching significantly lower values than the control at 90 s after tourniquet removal. This finding was supported by a greater half time for RBC aggregation in the samples obtained 60 and 90 s after tourniquet removal. In conclusion, this study revealed that RBC deformability and aggregation might be significantly altered in the samples obtained after the application and removal of a tourniquet, as a part of the blood sampling procedure. Recommendation "remove the tourniquet at least 5 s prior to the start of blood sampling" may need to be revised.

Effects of strenuous exercise on blood coagulation activity in sickle cell trait carriers.

We compared routine coagulation markers in six sickle cell trait carriers ((SCT, or AS hemoglobinopathy)--the heterozygous form of sickle cell anemia) and six subjects with normal hemoglobin before and after a prolonged and intense exercise. Blood was sampled at rest and at the end of the entire exercise test to measure coagulation markers (prothrombin time, activated partial thromboplastin time, plasma fibrinogen and antithrombin III activity), hematocrit (Hct) and yield stress (tau(y)). Results obtained at the end of exercise were corrected by the percent change in plasma volume. Blood coagulation markers, Hct and tau(y) were not different between the two groups at rest. Exercise did not change prothrombin time, antithrombin III activity and plasma fibrinogen, decreased activated partial thromboplastin time and increased Hct and tau(y) in the two groups. These parameters were not significantly different between the two groups at the end of exercise, except for plasma fibrinogen which was slightly higher in SCT carriers but in the normal range values. The results have been discussed in relation with some cases of exercise-related sudden death in SCT carriers, reported in several studies. Therefore our results show that the increased risk for clinical complications in certain SCT carriers during exercise seems to be unrelated to higher blood coagulation activity.

Hepatitis C virus (HCV) genotypes in the Caribbean island of Martinique: evidence for a large radiation of HCV-2 and for a recent introduction from Europe of HCV-4.

Molecular epidemiological studies of hepatitis C virus (HCV) in the Caribbean may help to specify the origin and spread of HCV infection. Indeed, the Caribbean population is intermixed from European and African origins and geographically close to the American continent. We characterized HCV genotypes in the Caribbean island of Martinique. HCV genotypes were analyzed by sequencing or reverse hybridization in the 5' noncoding region (5'NC) in 250 HCV-monoinfected and 85 HCV-human immunodeficiency virus (HIV)-coinfected patients. In addition, sequencing in the nonstructural 5B (NS5B) gene was required to determine the subtype or to perform phylogenetic analysis in selected samples. Genotypes 1 to 6 were found, respectively, in 84.4, 6.8, 5.2, 2.8, 0.4, and 0.4% of 250 HCV-monoinfected patients and in 71.7, 7.1, 15.3, 5.9, 0, and 0% of 85 HCV-HIV-coinfected patients. HCV-1b was found in 66.4% of the HCV-monoinfected patients and was associated with blood transfusion, whereas HCV-1a was detected in 41.2% of the HCV-HIV-coinfected patients and was associated with intravenous drug use (IVDU). The HCV-3 strains belonged to subtype 3a and were linked to IVDU. Phylogenetic analyses were focused on HCV-2 and HCV-4, which are common in Africa. Two opposite patterns were evidenced. NS5B sequences from 19 HCV-2 isolates were affiliated with many different subtypes described either in Europe or in West Africa, suggesting an ancient radiation. In contrast, seven of the nine HCV-4 NS5B sequences ranged within HCV-4a and HCV-4d clusters spreading in continental France by the IVDU route. Epidemiological data demonstrate the recent introduction of HCV-4a and -4d subtypes into the Caribbean.

Genital Chalmydia trachomatis (serotypes D-K) infection in Jamaican commercial street sex workers

OBJECTIVE: To determine in the prevalence of genital Chlamydia trachomatis infections in commercial street sex workers (CSSW) in Jamaica. METHODS: The prevalence of C trachomatis infection was determined in 129 Jamaican CSSW using the direct fluorescent antibody (DFA) method and the isolation techniques which utilise fluorescent and iodine staining of endocervical cytobrush specimens cultured in McCoy cells. The seroprevalence of C trachomatis in the CSSW was also compared with that in blood donors (n = 435), using the microimmuofluorescence (MIF) test. RESULTS: The DFA detect C trachomatis in 16 percent (21/129) of the specimens. The prevalence as determined by the iodine and fluorescein stained cultures was 24 percent (31/129) and 25 percent (33/129) respectively. The overall prevalence of current chalmydial infection detected by the isolation techniques used was 25 percent (33/129). As determined by the MIF test, a statistically significantly higher seroprevalence rate of C trachomatis (95 percent, 61/64) was found in CSSW compared with blood donors (53 percent, 229/435; OR 22.6; chi 2 = 49.8; p < 0.001). The prevalence of current infection in CSSW as indicated by the isolation of C trachomatis was not influenced by history of previous pelvic inflammatory disease (PID), sexually transmitted disease, or condom use. N gonorrhoeae (9 percent) and Candida albicans (7 percent) were found in comparatively low frequencies, while Trichomonas vaginalis (0 percent) was not found in specimens from the CSSW. CONCLUSIONS: A high seroprevalence rate and a high rate of current infection with C trachomatis occur in Jamaican CSSW. In order to control the spread and prevent the severe clinical complications and sequeles of C trachomatis infection, the diagnosis and treatment in such high risk groups such as CSSW should be optimised.(AU)

Seroprevalence of chlamydia trachomatis, hepatitis B and retroviruses in female STD patients and pregnant women in Jamaica - abstract

The seroprevalence of chlamydia trachomatis (Ct), hepatitis B (HBV), human immunodeficiency nirus (HIV) and human T-lymphotropic virus-type 1 (HTLV-I) was investigated in a high-risk group, patients from a sexually transmitted diseases clinic and prostitutes, as well as a low-risk group, antenatal group. In the STD group 100 sera were tested. Seropositivity for Ct was 82 percent,for HBsAg 3 percent, HBcAb 23 percent, HIV-Ab 2 percent and HTLV-1 Ab 8 percent. Among the 76 prostitutes, the seropsitivity was even higher: Ct 97 percent, HBsAg 8 percent, HBc,Ab 41 percent, HIV-Ab 9 percent and HTLV-1 Ab 17 percent. The antenatal women studied as a normal control population had lower levels: Ct 52 percent, HBsAg 0.7 percent, HBcAb 9 percent, HIV-Ab 0.7 percent and HTLV-1 Ab 2.8 percent. It is noteworthy that the seroprevalence for all the STDs investigated was markedly higher in the promiscuous group. Although the level for Ct antibodies was in the antenatal women, even this group showed a high prevalence of this very commonly occurring STD. (AU)

Chlamydia trachomatis infection in pregnant women in Martinique - abstract

Seven hundred and sixteen pregnant women attending the prenatal clinic at Lamentin Hopital, Martinique, were tested for chlamydia trachomatis (Ct) infection and risk factors associated with the infection. Samples for Ct isolation were taken from the endocervical canal and the urethra and cultured on cycloheximide-treated MacCoy cells. Ct inclusions are identified by monoclonal antibodies. Specific serum antibodies (Ab) were evaluated by an immunofluorescence method. Two hundred sixty-seven women (37.3 percent) had positive Ct culture, 34.5 percent from the cervix and 2.8 percent from the urethra alone. Comparing the group that did have Ct infection with the group that was not infected, the prevalence of the following factors was found to be significantly different (p<0.01): married (39.3 percent vs 27.2 percent), previous induced abortions (47.9 percent vs 30.8 percent), first intercourse at less than 18 years of age (43.3 percent vs 28.3 percent), more than two lifetime sex partners (40.9 percent vs 25 percent), friability of the cervix (45.3 percent vs 34.1 percent), polymorphonuclear neutrophils in cervical mucus (45.9 percent vs 26 percent), yellow endocervical discharge (44 percent vs 28 percent) concomitant trichomonas vaginalis (22.4 percent vs 15.8 percent), gardnerella vaginalis (19.8 percent vs 9.8 percent) and ureaplasma urealyticum (53.1 percent vs 34.5 percent) infection. Four-hundred and twenty women (58.8 percent) had Ct specific Ab. The mean level of Ab was lower in culture positive women (1/117) than in culture negative (1/272). The positive predictive value of Ab changed according to the age group (AU)