Association of hepatitis E seropositivity and altered progesterone levels in pregnant women of low socioeconomic status from capital region of Pakistan.

OBJECTIVE: To investigate the seroprevalence of hepatitis E virus infection, risk factors and its association with progesterone levels in pregnant women from low socioeconomic background. METHODS: The cross-sectional study was conducted in Rawalpindi and Islamabad, Pakistan, from January to July 2012, and comprised pregnant asymptomatic healthy females from different clinics and hospitals of the twin cities. Data was collected using a predesigned demographic questionnaire to determine socioeconomic status. Prevalence of anti-hepatitis E virus antibodies and progesterone levels were determined using enzyme-linked immunosorbent assay kits. RESULTS: Of the 90 women, 35(39%) were in the 21-25 year age group, and 55(61%) belonged to low socioeconomic background. The overall prevalence of seropositive hepatitis E virus immunoglobulin-G was 54(60%) and immunoglobulin-M was 12(13.3%). In the first trimester, the levels of progesterone were higher in patients positive for immunoglobulin-M compared to immunoglobulin-G (p<0.001). CONCLUSION: Low socioeconomic status appeared to be a potential risk factor associated with high hepatitis E virus seroprevalence and alterations in the normal progesterone levels during pregnancy.

Clinical and genetic studies in patients with Lafora disease from Pakistan.

Lafora disease (LD) is progressive myoclonic epilepsy with late childhood- to teenage-onset. Mutations in two genes, EPM2A and NHLRC1, are responsible for this autosomal recessive disease in many patients Worldwide. In present study, we reported two unrelated consanguineous Pakistani families with Lafora disease (Families A and B). Affected individuals in both families presented with generalized tonic clonic seizures, intellectual disability, ataxia and cognitive decline. Diagnosis of Lafora disease was made on histo-pathological analysis of the skin biopsy, found positive for lafora bodies in periodic acid schiff stain and frequent generalized epileptiform discharges on electroencephalogram (EEG). Bi-directional sequencing in family A was performed for EPM2A and NHLRC1 genes but no mutation was found. In family B, Illumina TruSight One Sequencing Panel covering 4813 OMIM genes was carried out and we identified a novel homozygous mutation c.95G>T; p.32Trp>Leu of EPM2A gene which was found co-segregated in this family through Sanger sequencing. Structural analysis of this mutation, through different in silico approaches, predicted loss of stability and conformation in Laforin protein.

Analysis of interleukin-10 gene polymorphisms and hepatitis C susceptibility in Pakistan.

INTRODUCTION: Hepatitis C virus (HCV) commonly causes a chronic infection but few of patients are able to clear the virus naturally. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that can suppress the immune response against HCV. Interindividual variations in IL-10 production are genetically contributed by polymorphisms within the IL-10 promoter region. This study aimed to investigate the association of the IL-10 gene promoter -1082 G/A, -819 C/T, and -592 C/A polymorphisms with HCV infection susceptibility in Pakistani individuals. METHODOLOGY: Eighty-nine chronically infected patients and 99 controls were enrolled in the study. IL-10 (-1,082 G/A, -819 C/T, -592 C/A) genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: A suggestive evidence of association with hepatitis C was obtained for the IL-10 -819 C/T (-592 C/A) (p: 0.03) promoter polymorphism at the allele level  but not in genotype distribution. The IL-10 -1082 allele showed no association while positive association of GG (p: 0.001) gene and negative association for GA (0.001) gene were observed.  Higher frequencies were observed for GTA (p: 0.02), ACC (p: 0.01) haplotype and GCC/GTA (p: 0.005) diplotype in HCV patients than controls while diplotype GCC/ATA showed protective effect against HCV. CONCLUSIONS: Our findings suggest that different IL-10 gene polymorphisms may lead to an imbalance between the pro-inflammatory and anti-inflammatory cytokine responses which may in turn influence the susceptibility to HCV infection.