Genome wide association study of uric acid in Indian population and interaction of identified variants with type 2 diabetes

Abnormal level of Serum Uric Acid (SUA) is an important marker and risk factor for complex diseases including Type 2 diabetes. Since genetic determinant of uric acid in Indians is totally unexplored, we tried to identify common variants associated with SUA in Indians using Genome Wide Association Study (GWAS). Association of five known variants in SLC2A9 and SLC22A11 genes with SUA level in 4,834 normoglycemics (1,109 in discovery and 3,725 in validation phase) was revealed with different effect size in Indians compared to other major ethnic population of the world. Combined analysis of 1,077 T2DM subjects (772 in discovery and 305 in validation phase) and normoglycemics revealed additional GWAS signal in ABCG2 gene. Differences in effect sizes of ABCG2 and SLC2A9 gene variants were observed between normoglycemics and T2DM patients. We identified two novel variants near long non-coding RNA genes AL356739.1 and AC064865.1 with nearly genome wide significance level. Meta-analysis and in silico replication in 11,745 individuals from AUSTWIN consortium improved association for rs12206002 in AL356739.1 gene to sub-genome wide association level. Our results extends association of SLC2A9, SLC22A11 and ABCG2 genes with SUA level in Indians and enrich the assemblages of evidence for SUA level and T2DM interrelationship

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients

علامہ اقبال بہ طور بچوں کے شاعر

Allama Iqbal was a multi-faceted personality. His poetry covered a wide range of topics for people from all walks of life. He was a poet not only of adults but also of children. According to Iqbal, today's children are tomorrow's youth and will be the vanguard of the Islam's future. The poetry Iqbal wrote for children has significance in children's literature today. Some of the poems in the early period were written especially for children. Many of these poems are derived from English poems. There are also some poems for children which were included in Waheed-ud-Din Faqir's book "Rozgar e Faqir" these poems were not included in any of Iqbal's collections. All these poems teach empathy, love, mysticism, humanity and humanity. He calls children and Muslim youth by the name of Shaheen because this bird has the characteristics of high flight, sharp eyesight, strong body and "Faqr". Iqbal also wrote an article titled "Children's Education and Training" and also developed school children's textbooks in which he has tried to highlight the best education as well as training aspects of children. In Iqbal's view, mental nurturing of children is an important need of the hour. The revolutionary message of Iqbal added depth to his words and promised a bright future for Muslim Youth.

Incidence, trends and morphology of ovarian cancer in Karachi (1995-2002).

Introduction:Cancer ovary is the third most common malignancy diagnosed in women in Karachi, a moderate to high risk region for the disease. Materials and Methods: Three hundred and thirty seven cases of ovarian cancer registered at the Karachi Cancer Registry for the years 1995-2002 were reviewed. Results: The age- standardized incidence rate (ASR) world per 100,000, crude incidence rate per 100,000 (CIR) and frequency of ovarian malignancies in 1995-1997 were 10.9, 5.9 and 6.2% respectively. Corresponding figures for 1998-2002 were 8.1, 5.1 and 4.8%. The mean age at presentation in 1995-1997 was 45.7 years (95%CI 42.9, 48.4, SD∓15.9), range 95 (3 to 98) years and in 1998-2002 it was 45.0 years (95%CI 42.8, 47.3, SD16.1), range 79 (3 to 82) years. Eleven (3.3%) cases of childhood cancers, 13 (3.9%) adolescent cases, 126 (37.4%) reproductive age (20-44 years) and 187 (55.5%) cases in the 45+ age group were registered. Epithelial malignancies were the most common cancers above the age of 20 years (78.4%), the commonest amongst these was serous adenocarcinoma (33.3%). Germ cell tumors were more common (5.6%) in children and adolescents. Microscopic confirmation was 99.0%. Presentation was of a moderately differentiated (grade 2) malignancy with a regional or distant spread of disease in three fourths of the cases. Conclusions: The incidence of cancer ovary, though stable in Karachi, involves a relatively younger age group with a strong family history in a fourth of the cases. The disease presents at an advanced stage. An ageing population over time may translate into a higher incidence of ovarian cancer. The current incidence of cancer ovary in Karachi is an enigma and belies reproductive protective factors. Studies focused on the genetic risk factors in this population are recommended

Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians

Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (N = 2158) and replication phase (N = 7935). We discovered two variants within/near the CETP gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional CETP loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the CETP locus constituting all seven CETP signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of SFRP1 gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome

Patho-epidemiology of Cancer Cervix in Karachi South

Introduction: The present study was conducted with the objective of examining descriptive epidemiological and pathological characteristics of cancer cervix in Karachi South, an all urban district population of Karachi, Pakistan. Methodology: A total of 74 cases of cancer cervix, ICD-10 (International Classification of Diseases 10th Revision) category C53 were registered at the Karachi Cancer Registry, for Karachi South, during a 3 year period, 1st January, 1995 to 31st December 1997. Results: The age standardized incidence rate (ASR) world andcrude incidence rate (CIR) per 100,000 were 6.81 (5.2, 8.43) and 3.22 (2.49 to 3.96). Cancer cervix accounted for approximately 3.6% of all cancers in females and was the sixth malignancy in hierarchy. The mean age of the cancer cases was 53.27 years [standard deviation (SD) 11.6; 95% confidence interval (CI) 50.58, 55.96; range(R) 32-85 years)]. The distribution by religion was Muslims (90.5%), Christians (8.1%) and Hindus (1.4%). There were no cases reported in Parsees. The frequency distribution by ethnicity was Urdu speaking Mohajirs (20.3%), Punjabis (17.6%), Gujrati speaking Mohajirs (4.1%), memon Mohajirs (8.1%), Sindhis (10.8%), Baluchs (8.1%), Pathans (5.4%) and Afghan migrants (2.7%). The ethnicity was not known in approximately a fourth (23.0%) of the cases.The socio-economic distribution was 27.0% financially deprived class, 24.4% lower middle class and 48.7% upper middle and affluent classes. The majority of the women were married (86.5%); a smaller number were unmarried (2.7%) or widows (10.8%). The age-specific curves showed a gradual increase in risk from the fourth up till the seventh decade, followed by an actual apparent decrease in risk after 64 years of age. The peak incidence was observed in the 60-64 year age group. The morphological categorization was squamous cell carcinoma (86.5%), adenocarcinoma (10.9%) and adenosquamous carcinoma (2.6%). The majority of cases presented with moderately differentiated or grade 2 lesions (45.9%). There were no in-situ cases. Approximately half the cancers (58.1%) had spread regionally and 8.1% to a distant site at the time of diagnosis. Odds ratios (OR) were calculated for socioeconomic residential categories, religion, ethnicity, age groups and education. The OR for socioeconomic residential categories ranged between 0.69 and 2.9 with a marginally higher risk in the lower [OR 2.09 (95% CI .97; 4.49)] and lower middle class [OR 2.08 (95%CI 0.95; 4.58)]. Hindus [OR 1.2 (95% CI 0.18; 2.2)] had a slightly higher risk then the Muslims [OR 0.14 (95% CI 0.17; 1.2)]. A higher risk was also observed for Christians [OR 7.76 (95% CI 1.74; 34.5)]. Conclusion: The incidence of cervical cancer in Karachi South (1995-97) reflects a low risk population with a late presentation and a high stage disease at presentation. It is suggested that cervical screening if implemented should focus on once a life time methodology involving 36-45 year old women. This should be combined with HPV vaccination for the young and public health education for all. A regular cervical screening program would require mobilization of considerable financial, structural and human resources along with training for personnel. This may burden the already stretched health resources of a developing country