Understanding of research: a Sri Lankan perspective

Background  

Lack of proper understanding on the part of researchers about public understanding of research and informed consent will increase the potential for malpractice. As a part of a larger study on ethics and informed consent in Sri Lanka, this study aimed to ascertain the level of understanding of 'research' by exploring the views of the public and professionals.     

Associations between HLA class II alleles in a North Indian population

Abstract: The HLA DR and DQ class II genes are in strong linkage disequilibrium and recombinaton is quite rare. However, many different DR-DQ haplotypes appear to have developed during evolution, giving rise to a variety of combinations with different distributions in populations. In the present report, 138 subjects from North India were studied for the alleles of HLA-DRB1, DRB3, DRB5, DQB1 and DQA1 loci using PCR-oligotyping. The probable haplotypes were constructed based on two-locus associations observed in this population. A frequent haplotype in this population, DRB1*1501-DRB5*0101-DQA1*0103-DQB1 *0601, has been reported very rarely in other ethnic groups. Other DR2 haplotypes, like DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601, earlier reported in Caucasians, Chinese and Latin Americans, and DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0503, earlier reported in Gypsies, were also observed. A relatively rare haplotype in Caucasians which was earlier reported in Gypsies from the Czech Republic, DRB1*1404-DRB3*0202-DQA1*0101-DQB1*0503, was observed frequently in Indians, suggesting the probable migration of Gypsies from India. The results suggest that the North Indian population contains a mixture of Caucasoid, Black and Chinese genes. Similarities with Gypsies and South-East Asian populations suggest the role of ancient migrations from India.     

HLA haplotypes associated with type 1 diabetes mellitus in North Indian children

Human leukocyte antigen (HLA) encoded susceptibility to develop type 1 diabetes mellitus (T1DM) has been investigated in children from North India. The results revealed significantly increased prevalence of HLA-A26, -B8, and -B50 among patients and strong positive association of the disease with DRB1*0301 (82.1% vs 13.9%, chi2=71.3, odds ratio [OR]=28.3) and a negative association with DRB1*02 (chi2=12.2, PF=38.5). HLA-DQB1*0201 occurred in 96.4% of the patients, whereas the heterodimer DQA1*0501-DQB1*0201 was present in 82.1% of patients (60.7% in single dose and 21.4% in double dose) and revealed significant deviation from the healthy controls (chi2=74.1, pc=6.0E-10). In addition to DRB1*03, positive association was also observed with DRB1*09 (14.3% vs 1.3%, chi2=13.4) and DRB1*04 (39.3% vs 15.6%, chi2=8.39). No HLA association was observed in relation to residual pancreatic beta-cell function or associated thyroid autoimmunity. Family analysis revealed involvement of multiple DR3+ve haplotypes with T1DM in North Indian children with A26-B8-DRB1*03 (25% vs 3.5%, chi2=16.9, p=3.96E-05) and Ax-B50-DRB1*03 (25% vs 0.7%, chi2=44.7, p=9.88E-11) being the most frequent haplotypes encountered among patients. The classical Caucasian haplotype A1-B8-DRB1*03 was infrequent (7.2%) among the diabetic children. The study highlights the race specificity of HLA association and disease associated HLA haplotypes in T1DM among North Indian children.     

Distribution of HLA antigens in a sample of the North Indian Hindu population

The Indian population can be divided broadly into Dravidians and the Aryans. In this report, we have attempted to analyze the HLA genetic profile of 400 native North Indian Hindus of Aryan descent. The gene frequencies of a majority of class I and II antigens show similarity to the Caucasoid population. An interesting finding was a complete lack of antigen B14 while B16 and B41 occurred with the least frequency. Haplotype A10, B8 with significant positive linkage disequilibrium as well as showing the highest incidence is characteristic of North Indians.     

Validity of newly-developed BMI and waist cut-off values for Sri Lankan children

Background: Excess body fat leads to obesity-related morbidity and population/ethnicity-specific cut-off values of anthropometric measures are useful for better diagnosis. This study assesses the suitability of newly-developed Sri Lankan anthropometric cut-off values in the diagnosis of obesity in Sri Lankan children.

Methods: A cross-sectional study was conducted at University of Colombo, Sri Lanka involving 5–15 year old children. Height, weight, waist (WC), and hip (HC) circumferences were measured. Total body fat (FM) was measured using whole body BIA. WHR and WHtR were calculated. Validity of anthropometric measures in detecting childhood obesity (Sri Lankan BMI/WC; IOTF, WHO, British and CDC BMI and British WC cut-off values) were evaluated.

Results: Nine hundred and twenty children were assessed. FM showed significant associations with BMI (r = 0.92, p < 0.001), WC (r = 0.90, p < 0.001) and HC (r = 0.85, p < 0.001), but poor association with WHR (r = 0.17, p < 0.001). However, WHtR had a high association with FM (r = 0.75, p < 0.001) and %FM (r = 0.78, p < 0.001). Based on %FM cut-offs, 85 (22.8%) girls and 101 (18.5%) boys were obese. All international anthropometric cut-off values under-estimated obesity. Sri Lankan WC and BMI cut-off values over-estimated obesity. International BMI based cut-off values had high specificity (>99%) but a low sensitivity (～12–33%), while Sri Lankan BMI cut-off values had high sensitivity (>93.1) but low specificity (>79.7).

Conclusions: Internationally available BMI cut-off values are poor in diagnosing obesity in Sri Lankan children. Newly developed Sri Lankan BMI cut-off values for children improved the diagnosis. WC can be used successfully as an alternative diagnostic tool of obesity.     

Accumulation of lipoprotein pigments in nerve cells of British and Sri Lankan nationals

The lipofuscin and melanin contents of nerve cells were measured in 18 subjects, 9 of British Nationality, 9 of Sri Lankan, both groups being matched for age and sex. Lipofuscin content was apparently increased for age in the British group, though melanin content was unchanged. Nucleolar volume was unaltered in both groups for all cell types. It is suggested that the lipid portion of the lipofuscin granule is increased in the British cases, rather than the actual mass of pigment granules, and that this change in composition may be related to differences in diet, particularly in respect of the amount of polyunsaturated fat consumed by the two populations.     

Both Indian cassava mosaic virus and Sri Lankan cassava mosaic virus are found in India and exhibit high variability as assessed by PCR-RFLP

Summary. The biodiversity of geminiviruses associated with the Cassava Mosaic Disease (CMD) in India was investigated using PCR to specifically amplify the DNA of Indian cassava mosaic virus (ICMV) or Sri Lankan cassava mosaic virus (SLCMV) and also by using PCR to amplify specific viral genes, followed by digestion with different restriction endonucleases to obtain polymorphic patterns (PCR-RFLP). Results showed that both ICMV and SLCMV were present in mosaic-affected cassava; ICMV was geographically restricted to certain regions, whereas SLCMV was widespread. PCR-RFLP analysis showed that, in addition to ICMV-type and SLCMV-type patterns, a high proportion (40%) of the samples displayed novel patterns, some of which were localized in certain areas, whereas others were widely distributed.     

Single occasion means of height and weight of Sri Lankan Tamil children from Jaffna

Little published material is available on physical growth in any Sri Lankan population. This paper reports attained mean heights and weights of middle class Tamil children from Jaffna, based on single occasion measurements of 358 boys and 517 girls ranging in age between 6 and 17 years. The cross-sectional height and weight data of both boys and girls show a typical pattern. Boys are taller and heavier up to 9 years, then girls lead in both the meassurements due to their pubertal phase of rapid growth. Boys supersede them again when they enter into their rapid growth phase, i.e. in height at 13 years but their mean weights remain lower till 16 years. Thus at 17 years boys on average are 5 cm taller than girls. With reference to British standards the attained means of both boys' and girls' height remain around the 10th centile, but later shift to the 3rd centile. In weight, however, they remain below the 3rd centile and indeed much below the range during the later part of the pubertal phase. Apart from nutrition and living conditions, how much of this pattern is influenced by ethnic and tropical climatic factors is still unclear.     

Characterisation of Sri Lankan cassava mosaic virus and Indian cassava mosaic virus: evidence for acquisition of a DNA B component by a monopartite begomovirus

Two bipartite begomoviruses, Indian cassava mosaic virus (ICMV) and Sri Lankan cassava mosaic virus (SLCMV), have been isolated from mosaic-diseased cassava originating from central India and Sri Lanka, respectively. ICMV was transmitted with low efficiency from cassava to Nicotiana benthamiana by sap inoculation to give leaf curl symptoms. SLCMV was much more virulent in this host, producing severe stunting, leaf curl, and chlorosis. These symptoms were reproduced when their cloned genomic components (DNAs A and B) were introduced into N. benthamiana by either mechanical or Agrobacterium-mediated inoculation (agroinoculation). SLCMV is more closely related to ICMV (DNA A, 84%; DNA B, 94% nucleotide identity) than African cassava mosaic virus (ACMV) (DNA A, 74%; DNA B, 47% nucleotide identity). Sequence comparisons suggest that SLCMV DNA B originated from ICMV DNA B by a recombination event involving the SLCMV DNA A intergenic region. Pseudorecombinants produced by reassortment of the cloned components of ICMV and ACMV were not infectious in N. benthamiana, emphasising their status as distinct virus species. In contrast, a pseudorecombinant between ACMV DNA A and SLCMV DNA B was infectious. Consistent with these observations, iteron motifs located within the intergenic region that may be involved in the initiation of viral DNA replication are conserved between SLCMV and ACMV but not ICMV. When introduced into N. benthamiana by agroinoculation, SLCMV DNA A alone produced a severe upward leaf roll symptom, reminiscent of the phenotype associated with some monopartite begomoviruses. Furthermore, coinoculation of SLCMV DNA A and the satellite DNA beta associated with ageratum yellow vein virus (AYVV) produced severe downward leaf curl in N. glutinosa and yellow vein symptoms in Ageratum conyzoides, resembling the phenotypes associated with AYVV DNA A and DNA beta infection in these hosts. Thus, SLCMV DNA A has biological characteristics of a monopartite begomovirus, and the virus probably evolved by acquisition of a DNA B component from ICMV.     

Single occasion means of height and weight of Sri Lankan Tamil children from Jaffna

Little published material is available on physical growth in any Sri Lankan population. This paper reports attained mean heights and weights of middle class Tamil children from Jaffna, based on single occasion measurements of 358 boys and 517 girls ranging in age between 6 and 17 years. The cross-sectional height and weight data of both boys and girls show a typical pattern. Boys are taller and heavier up to 9 years, then girls lead in both the measurements due to their pubertal phase of rapid growth. Boys supersede them again when they enter into their rapid growth phase, i.e. in height at 13 years but their mean weights remain lower till 16 years. Thus at 17 years boys on average are 5 cm taller than girls. With reference to British standards the attained means of both boys' and girls' height remain around the 10th centile, but later shift to the 3rd centile. In weight, however, they remain below the 3rd centile and indeed much below the range during the later part of the pubertal phase. Apart from nutrition and living conditions, how much of this pattern is influenced by ethnic and tropical climatic factors is still unclear.     

Kerion celsi due to Arthroderma incurvatum infection in a Sri Lankan child: species identification and analysis of area-dependent genetic polymorphism

A three-year-old Sri Lankan boy residing in Japan developed a nodule on his scalp after visiting Sri Lanka. Two months later, the lesion increased in size to 22 × 19 mm(2), and was identified as an erythematous nodule with alopecia. Direct examination of the infected hair shafts indicated fungal hyphae outside the shafts. The fungus was identified as Microsporum gypseum following mycological examination. The sequence of the internal transcribed spacer 1 region of ribosomal RNA gene (ITS1 rDNA) exhibited 95.7-100.0% homology with that of Arthroderma incurvatum. The patient was successfully treated with a 6-week itraconazole course. We also examined DNA samples from eight clinical isolates of A. incurvatum. Alignments of ITS1 sequences of these strains and our isolate, showed gaps in the 64-bp positions 140-142 and 141-143 of the 205-207-bp ITS1 alignment. We performed phylogenetic analysis using the neighbor-jointing (NJ) method based on the ITS1 sequences of the present isolate and twenty related strains. Fifteen A. incurvatum strains were divided into East Asia and non-East Asia clusters. The present isolate belonged to the non-East Asia cluster, suggesting that the patient was infected outside Japan. Moreover, the trees suggested area-dependent genetic polymorphism of A. incurvatum.     

HLA alleles in isolated populations from North Spain: origin of the Basques and the ancient Iberians

HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles have been studied in three relatively isolated populations of northern Spain from Cantabria ( Pas Valleys inhabitants or Pasiegos and Cabuernigos) and from the Basque Country (Arratia Valley inhabitants). These populations have been compared with neighbouring ones and other Mediterraneans by using neighbour-joining dendrograms and plane genetic distances.     

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in Thai, Sri Lankan and Paraguayan populations

The genetic polymorphism of orosomucoid (ORM) and alpha-2-HS-glycoprotein (AHSG) were studied in Thai, Sri Lankan and Paraguayan populations using isoelectric focusing. Gene frequencies in these populations were compared with those in other populations. Four new ORM variants were detected: ORM1*15 in Thai, ORM1*16 in Paraguayan, ORM2*21 and ORM2*22 in Sri Lankan.     

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in Thai,Sri Lankan and Paraguayan populations

The genetic polymorphism of orosomucoid (ORM) and alpha-2-HS-glycoprotein (AHSG) were studied in Thai, Sri Lankan and Paraguayan populations using isoelectric focusing. Gene frequencies in these populations were compared with those in other populations. Four new ORM variants were detected:ORM1 ^* 15 in Thai,ORM1 ^* 16 in Paraguayan,ORM2 ^* 21 andORM2 ^* 22 in Sri Lankan.     

Validity of BMI as a measure of obesity in Australian white Caucasian and Australian Sri Lankan children

BACKGROUND: Body mass index (BMI) is used to diagnose obesity. However, its ability to predict the percentage fat mass (%FM) reliably is doubtful. Therefore validity of BMI as a diagnostic tool of obesity is questioned. AIM: This study is focused on determining the ability of BMI-based cut-off values in diagnosing obesity among Australian children of white Caucasian and Sri Lankan origin. SUBJECTS AND METHODS: Height and weight was measured and BMI (W/H2) calculated. Total body water was determined by deuterium dilution technique and fat free mass and hence fat mass derived using age- and gender-specific constants. A %FM of 30% for girls and 20% for boys was considered as the criterion cut-off level for obesity. BMI-based obesity cut-offs described by the International Obesity Task Force (IOTF), CDC/NCHS centile charts and BMI-Z were validated against the criterion method. RESULTS: There were 96 white Caucasian and 42 Sri Lankan children. Of the white Caucasians, 19 (36%) girls and 29 (66%) boys, and of the Sri Lankans 7 (46%) girls and 16 (63%) boys, were obese based on %FM. The FM and BMI were closely associated in both Caucasians (r=0.81, P<0.001) and Sri Lankans (r=0.92, P<0.001). Percentage FM and BMI also had a lower but significant association. Obesity cut-off values recommended by IOTF failed to detect a single case of obesity in either group. However, NCHS and BMI-Z cut-offs detected cases of obesity with low sensitivity. CONCLUSIONS: BMI is a poor indicator of percentage fat and the commonly used cut-off values were not sensitive enough to detect cases of childhood obesity in this study. In order to improve the diagnosis of obesity, either BMI cut-off values should be revised to increase the sensitivity or the possibility of using other indirect methods of estimating the %FM should be explored.     

Validity of BMI as a measure of obesity in Australian white Caucasian and Australian Sri Lankan children

Background: Body mass index (BMI) is used to diagnose obesity. However, its ability to predict the percentage fat mass (%FM) reliably is doubtful. Therefore validity of BMI as a diagnostic tool of obesity is questioned. Aim: This study is focused on determining the ability of BMI-based cut-off values in diagnosing obesity among Australian children of white Caucasian and Sri Lankan origin. Subjects and methods: Height and weight was measured and BMI (W/H²) calculated. Total body water was determined by deuterium dilution technique and fat free mass and hence fat mass derived using age- and gender-specific constants. A %FM of 30% for girls and 20% for boys was considered as the criterion cut-off level for obesity. BMI-based obesity cut-offs described by the International Obesity Task Force (IOTF), CDC/NCHS centile charts and BMI-Z were validated against the criterion method. Results: There were 96 white Caucasian and 42 Sri Lankan children. Of the white Caucasians, 19 (36%) girls and 29 (66%) boys, and of the Sri Lankans 7 (46%) girls and 16 (63%) boys, were obese based on %FM. The FM and BMI were closely associated in both Caucasians (r?=?0.81, P<0.001) and Sri Lankans (r?=?0.92, P<0.001). Percentage FM and BMI also had a lower but significant association. Obesity cut-off values recommended by IOTF failed to detect a single case of obesity in either group. However, NCHS and BMI-Z cut-offs detected cases of obesity with low sensitivity. Conclusions: BMI is a poor indicator of percentage fat and the commonly used cut-off values were not sensitive enough to detect cases of childhood obesity in this study. In order to improve the diagnosis of obesity, either BMI cut-off values should be revised to increase the sensitivity or the possibility of using other indirect methods of estimating the %FM should be explored.     

A study of HLA-B115:02 in a Sri Lankan population: Implications for pharmacogenomic testing

HLA-B115:02 is known as a biomarker for carbamazepine (CBZ) induced Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) in some Asian populations. Hence United States Federal Drug Administration (USFDA) recommends HLA-B115:02 screening for Asian and other populations with a high prevalence of HLA-B115:02, prior to the administration of carbamazepine. This study was conducted to estimate the prevalence of HLA-B115:02 in a cohort of Sri Lankans. We observed an overall prevalence of 4.3% (4/93) among 93 Sri Lankans comprising 32 Sinhalese, 30 Sri Lankan Tamils and 31 Moors. The allele was detected in 3 [9.3%; 3/32] Sinhalese, 0 [0%; 0/30] Sri Lankan Tamils and in 1 [3%; 1/31] Moor. The overall prevalence of HLA-B115:02 in this population was close to that of other populations where the USFDA has recommended HLA-B115:02 screening. A larger study is required to confirm these findings, especially among the Sinhalese where the frequency appears to be high.