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Home > Molecular Genetic Analysis of Susceptible Diabetic Nephropathy Genes in Type 2 Diabetics

Molecular Genetic Analysis of Susceptible Diabetic Nephropathy Genes in Type 2 Diabetics

Thesis Info

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Author

Zain, Maryam

Program

PhD

Institute

Pakistan Institute of Engineering and Applied Sciences

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2014

Thesis Completion Status

Completed

Subject

Applied Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/2130/1/2383S.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726704765

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Diabetic Nephropathy (DN) is a major complication of both type 1 and type 2 diabetes and a leading cause of mortality due to End Stage Renal Disease (ESRD) worldwide. This overwhelming clinical problem is also affecting a number of diabetic patients in Pakistan. Several molecular pathways could lead to the development of DN. In this thesis, the role of genes in one classical pathway, the Renin Angiotensin Aldosterone System (RAAS) along with fatty acid metabolism, and cardiovascular related pathways were investigated in type 2 diabetics, nephropathy and ESRD cohorts. The aim was to see the allele and genotype frequency differences of Pakistani, French and UK population. The study is divided into three parts for Pakistani, French and UK cohorts. For Pakistani Punjabi population, 206 subjects mainly from the Faisalabad district were included. The study design comprised of four groups which were analyzed for biochemical and molecular characterization. PCR and PCR-RFLP based genotyping assays followed by Real Time PCR technique (TaqMan Assay) were carried out for the ACE, AGT, CYP11B2 and ACACB genes to identify the genotypes of each group individually, and calculate and compare their genotype frequencies among four groups as well with individual non-genetic parameters in each group. The association of genotypes was analyzed for their correlation with all of the biochemical parameters, as well as with hypertension, family history of diabetes and nephropathy status. The results showed the association of CYP11B2 gene polymorphism (T/C) with diabetes with OR (95%CI, P value) of 3.20 (1.15-8.91, 0.02), and a significant association of ACACB gene polymorphism (G/A) with obesity/BMI (P =0.009) and type 2 diabetes (P=0.02). For French cohorts, one of the genes of fatty acid metabolism pathway i.e. ACACB (G/A) was analyzed in five different cohorts (n=7438) of diabetic patients who were at various stages of nephropathy. The genotypes were compared for ethnic variations as well as association for different parameters. Results showed a significant association (P=0.02) with ESRD. For UK population, the association study of cardiovascular and hypertension related SNPs in LPA, DAB2IP and TLL1 genes with baseline characteristics or disease outcomes in four UK cohorts (n=5602) was performed. Results showed LPA SNPs association with serum Lp(a) levels in one of the cohorts (NPHS-II group), whereas for DAB2IP SNP (rs7025486), the significant association with High Density Lipoprotein levels (P=0.01) and Diastolic Blood Pressure (P=0.03) was observed. From this study, it is suggested that if similar studies are carried out on large number of samples (replication and meta-analysis), it will be helpful in identifying genetic biomarkers for DN on the basis of ethnic variations and devising pharmacogenomics based interventions.
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امام خمینی

امام خمینی
حق مغفرت کرے عجب آزاد مرد تھا
انقلاب ایران کے تاریخ ساز قائد، ایران میں اسلامی جمہوریہ کے بانی، روحانی پیشوا اور عالمِ اسلام کے ایک عظیم فرزند علامہ روح اﷲ آیت اﷲ خمینی مرحوم ۳؍جون بروز شنبہ کواپنی علالت اورآپریشن میں ناکامی کے بعد بالآخر وہاں پہنچ گئے جہاں ہم میں سے ہرایک کوایک دن جانا ہے۔ اِنَّالِلّٰہِ وَاِنَّا اِلَیْہِ راجِعُوْن۔علامہ خمینی کے انتقال کی خبر سے مسلم ممالک میں صفِ ماتم بچھ گئی، موت اَٹل اوربَرحق ہے اور یہ تلخ گھونٹ ہر متنفّس کواپنے وقت پر پینا ہے۔’’کل نفسٍ ذائقۃُ الموت‘‘ اور ’’اِذَا جَآء اجُلُھَا لَا ےَسْتَاخِرُون ساعۃ وَلَا یستقدمون ‘‘ فرمان الٰہی ہے۔
تاہم اس کار گاہِ ہستی میں بعض شخصیات ایسی بھی پیدا ہوتی ہیں، جن کے دنیا سے اُٹھ جانے کے بعد جوخلاء پیداہوتا ہے،اس کاپُر ہونا ممکن نہیں ہوتا ہے۔ یہ حقیقت ہے کہ موجودہ صدی میں جن اہم شخصیات نے جدید تاریخ پرگہرے نقوش واثرات چھوڑے ہیں، اور ایک لمبی مدت تک جن کی یاد باقی رکھی جائے گی ان میں مرحوم رہنما کی انقلاب آفریں ذات بھی شامل ہے۔
بلاشبہ علامہ خمینی کے انتقال سے سیاسی بالغ نظری، جرأت،بے باکی انقلاب، عزم اور خودداری کے ایک دور کاخاتمہ ہوگیا، علامہ خمینی اپنی ذاتی خصوصیات اوصاف اور کمالات کے اعتبار سے ایک پُرکشش، باوضع اوربھاری بھرکم شخصیت کے مالک تھے ان کے بعض عقائد وافکار ونظریات ،سیاسی سوچ و اپروچ اور طریقِ کارسے جمہوری اختلاف کے باوجود ان کی اصول پسندی، جذبۂ حرّیت ،ایثار وقربانی اور جدوجہد کی تعریف کیے بغیر چارۂ کار نہیں ہے۔
علامہ آیت اﷲ خمینی ۱۹۰۰ء میں شمالی ایران کے جران نامی ایک قصبہ خمین میں پیدا ہوئے، کل عمر ۸۹؍ سال کی پائی، بچپن سے ہی آپ کی تعلیم وتربیت ایک خاص ماحول میں ہوئی۔آپ نے اسلامیات ،دینیات ،فقہ اور فلسفہ کے شعبوں...

The Aims of the Prophetic Hijrah and its Teaching and Guidance

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Adaptation, Modification and Development of Norms of Hand Test in Pakistan

The present study aims to Adapt, modify and develop norms of the Hand Test in Pakistan. A sample of 500 participants (270 males & 230 females) age ranged from 11 to 80 years (M=34.44 & SD=17.34) was recruited from various cities of Pakistan. The sample belonged to various economic classes which includes earnings from up to 20,000 to above 1 lac Pakistani Rupees. Participants were further bifurcated into four groups which include 350 normal who were further divided age wise into four groups. Group one age ranged from 11 to 20 years. Group two age ranged from 21 to 40 years. Group three age ranged from 41 to 60 years. Group four 61 years and above. The second group consisted of 50 maladjusted. The third group consisted of 50 neurotic/anxiety related disorders who were categorized into generalized anxiety, obsessive compulsive and phobic. Whereas, the fourth group consisted of psychotics who were further categorized into schizophrenic, major depression and bipolar. Cross sectional research design was implied, purposive sampling technique was used for data collection. The study was carried out phase wise, in phase one scoring booklet of Hand Test (Wagner, 1983) was translated from English into Urdu language using back translation method, comprising fourteen stimuli (10 original and Four adapted). A pilot study was carried out to adapt four new stimuli out of a set of 10 on the criterions (a) their ability to generate responses in more scoring categories (b) varied range of responses and these were placed from stimuli nine to thirteen. Licence to use the Modified Hand Test was obtained from Western Psychological Services. In phase two reliability and validity studies were carried out to establish psychometric properties of the Modified Hand Test with promising results test-retest reliability (r =.39 to .83), inter-scorer reliability (r =.87), split- half reliability was determined while dividing stimuli into odd and even categories and it was found in the range of α=.04 to .84 for failure (in neurotic/anxiety related disorder group) to bizarre (in psychotic group). Construct Validity came out for interpersonal with environmental (r =.43). Predictive validity of socially desirable traits with academic grades remained moderate. In phase three normative data, percentile ranks and z scores were computed for various scoring categories which facilitated in determining normal ranges of scores across group of samples for age groups and gender for normal group. Qualitative analysis based on content was computed through frequency counts; certain new areas were explored like religiosity, oppositional, introjection, projection need for altruism and affiliation. One-way analysis of variance (ANOVA) was computed for different groups of participants, age groups and economic classes for normal group. Results were significant across main domains as well as sub categories at .01 and .05 level of significance. Analysis of results depicted that the Modified Hand Test provided confirmation to normative data and studies reported by its author and other researchers. Furthermore, it explored new dimensions of personality.