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Genetic Studies of Cardiovascular Diseases

Thesis Info

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Author

Waqas Ahmed

Program

PhD

Institute

COMSATS University Islamabad

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2012

Thesis Completion Status

Completed

Subject

Natural Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/225

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726311285

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the underdeveloped countries like Pakistan, leading to socioeconomic destabilization of the community. Among the different factors that play a role in the onset and progression of disease, raised plasma cholesterol levels is considered to be a major factor in the development of atherosclerosis, a typical character for the development of CVDs. Candidate gene screening of hypercholesterolemia families and sporadic individuals revealed two mutations in LDL-C binding domain (La) of LDLR (c.264G>C, p.R88S and c.887_889GCA>AGC, p.296*), four missense mutations in EGF like domain (c. 1019_1020delinsTG, p.C340L; c.1211C>T, p.T404I; c.1214 A>C, p.N405T; c.1634G>A, p.G545E and c.1916T>G, p.V639) and one premature terminating mutation (c.2416_2417 Ins G, p.V806GfsX11) in the transmembrane domain of LDLR. The La domain mutation has been shown to lead to inefficient binding of LDL-C with the receptor, while mutations in EGF like domain were found to cause decreased recycling of LDLR to the hepatocytes surface, which resulted in raised cholesterol levels in the patients. Two variants in PCSK9 i.e., c.314G>A, p.R105Q and c.464C>T, p.P155L, were also found in two different families with a history of CABG. The variant c.314G>A, p.R105Q resulted in 19% decrease in LDL-C levels in heterozygote carriers compared to homozygote normal individuals predicting it to be a “loss of function mutation”, while the second variant c.464C>T, p.P155L was located in the autocatalytic site of PCSK9 which may impact on LDL-C, but its exact effect could not be determined due to the small family size. In case control studies on MI cases in Pakistani population, the screening of selected panel of single nucleotide polymorphisms (SNPs) within five different genes was conducted. It was found that rs1333049 (ANRIL) was significantly associated with the onset of disease (p<0.001), while rs10920501 (FAM5C), rs1042579 (THBD), rs4646994 (ACE) and Intron 4 VNTR (eNOS) were not associated with the onset of MI (p>0.05). The stratification of data based on coronary artery disease (CAD) family history revealed significant association of the risk allele in ACE and eNOS polymorphisms with OR 1.83(95% CI=1.06-3.14) and 1.82(95% CI=1.03-3.22), respectively. This also indicates that the clustering of genetic factors within the ixfamilies are responsible for the onset of MI in Pakistani families. The relationship of rs1333049 risk allele “C” with phenotype impact on the lipid profile also showed a marked decrease in total cholesterol in individual homozygous for risk allele, which was observed in an independent cohort of hypercholesterolemia patients from the affected families as compared to their normolipidemic individuals. From this study, it is revealed that the Pakistani population has genetic heterogeneity, which predisposes the individuals to an increased risk of MI.
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مولانا عبدالسلام ندوی

مولانا عبدالسلام ندوی
گزشتہ مہینہ مولانا عبدالسلام ندوی کی وفات اردو زبان کے علمی اورادبی حلقوں کے لیے ایک بڑا الم ناک سانحہ ہے۔مرحوم کاسب سے بڑاوصف اور کمال جس میں مشکل سے ہی کوئی اُن کاحریف ہوگایہ تھا کہ وہ صرف ایک نامور مصنف، بلندپایہ ادیب اورنقد سخن کے بہترین جوہری تھے، اس حیثیت سے وہ لیلی علم وادب کومخاطب کرکے بجاطورپر کہہ سکتے تھے کہ :
’’سب سے بیگانہ ہے اے دوست شناسا تیرا‘‘
۱۹۲۸ء میں امرتسر میں ندوۃ العلماء کے سالانہ جلسہ کے موقع پر راقم الحروف کو مولانا ابوالجلال ندوی اورمولانا نورالحق ندوی جواُس وقت نئے نئے مصر سے واپس آئے تھے ان دونوں کی معیت میں مولانا مرحوم سے ملاقات کا پہلا اورآخری بھی، شرف حاصل ہوا تھا۔یہ ملاقات جس طرح ہوئی،مولانا کو جس وضع قطع میں دیکھااوراُن سے جو گفتگو ہوئی، اگرکوئی اورہوتاتویقینا بدگمان ہوجاتالیکن میرے دل پراُس کاخاص اثر ہوا اوراُن کے فطری مصنف اورادیب ہونے کا جزم ہوگیا اوربے ساختہ زبان سے تمکین دہلوی کایہ شعر نکل گیا:
آنکھ پڑتی ہے کہیں پاؤں کہیں پڑتا ہے
سب کی ہے تم کو خبر، اپنی خبر کچھ بھی نہیں
مرحوم کی عبارت سادہ مگر شگفتہ اوربہت سلجھی ہوئی ہوتی تھی۔ جس موضوع پرگفتگو کرتے تھے اُس کے تمام پہلوؤں کامکمل تجزیہ کرکے ہرپہلو پرسیرحاصل بحث کرتے تھے، اس لیے اُن کاطرزنگارش صرف پڑھنے میں دلچسپ ودل نشین نہیں تھا بلکہ یقین آفرین بھی تھا۔مولانا شبلی نے اپنے شاگرد کے اس وصف طبعی کو پہلے ہی تاڑلیا تھا اوروہ اس کے بڑے قدران تھے۔چنانچہ اُن کے مکاتیب میں مرحوم کی نسبت جو حوصلہ افزاتاثرات وخیالات ملتے ہیں وہ اُن کے کسی دوسرے شاگرد یہاں تک کہ سید صاحب کے متعلق بھی نہیں ملتے۔ بیسوں مقالات کے علاوہ مرحوم کی مستقل تصنیفات تاریخ وفلسفہ،اخلاق،شعروادب اورتنقید سے متعلق ہیں،اردو ادب کاایسا قیمتی سرمایہ ہیں...

مشترک الفاظ ِ قرآنیہ کی توجیہات و تفسیرات

Mushtarak” is a word used for those words that are used in the Holy Qura’n with more than one meaning. These words are a manifestation of Quranic eloquence. They show the diversity of Qur'anic meaning, as well as the differences in their definitions, which have led to interpretation differences in the Qur'an. Due to the common words, the interpretation in the jurisprudence and the opinion of the scholars had expanded. Some interpretive deviations have also been related to these words. The study of the textual literature is important in this context that all discussions of common words should be discussed and the principles of meaning determination should be clearly presented with arguments as well. The contemporary commentaries in which different interpretations have been made from them would also be analyzed. This research would try to provide a narrative on finding  the meaning of such words and the limits within which the different interpretation can be done.

Potential of Microbial Insecticides and Diatomaceous Earth Against Three Coleopterous Insect Pests of Stored Grains under Different Abiotic Conditions

Sitophilus granarius (L.), Rhyzopertha dominica (F.) and Oryzaephilus surinamensis (L.) are the damaging insect pests of cereals and their commodities and are able to cause significant losses. Current research was performed to evaluate the lethal and progeny inhibition effect of microbial-based insecticides i.e entomopathogenic fungi (EPF) Metarhizium anisopliae and Beauveria bassiana as well as bacterial based insecticides (spinetoram and abamectin) solitary andwith combination of two formulations of diatomaceous-earth (DE) against S. granarius, O. surinamensis and R. dominica. Three concentrations (1x108, 1.5x108 and 2x108 spores/kg grain) of each EPF were used while for bacterial based insecticides concentrations were 0.5, 1.0 and 1.5ppm. Similarly, for diatomaceous earth, three different doses (200, 400 and 800 ppm) of every formulation were applied. Completely Randomized Design (CRD) was used with three repetitions of all treatments. Mortality of test insects was recorded after 7, 14 and 21 days while after 60 days for post-treatment progeny build up. Each bioassay was performed at three levels of temperature (25°, 30° and 35°C) and relative humidity (r.h.; 45, 60 and 75%). Collected statistics were examined with applicable statistical methods using R-Software.The data analyses had shown diversified results regarding test insect susceptibility at different abiotic conditions. In case of Bacterial based insecticides, the response of treatment remained best at high temperature and low r.h. for all test insects. Complete control was achieved after 14 days for S. granarius and R. dominica while for O. surinamensis 100% mortality was not attained even after 21-d of exposure period. Progeny production was remained totally suppressed for S. granarius and R. dominica while in case of O. surinamensis there was significant reproduction at some abiotic conditions with maximum production at temperature of 30°C with 75% r.h. The response of-D.E against test insects was also effective and the most vulnerable species was O. surinamensis followed by S. granarius and R. dominica. It was observed that high temperature, low r.h. levels, higher dosages and long exposure periods increased the efficacy of DEs. Regarding progeny production, low temperature and high humidity remained most favourable for progeny emergence in DE-treated grains. The effects of EPF remained somewhat similar to the response of DE but overall mortality was low. Among tested species of insects R. dominica remained most susceptible to the application of EPF followed by O. surinamensis and S. granarius. The best abiotic condition for B. bassiana was low temperature (25°C) and moderate (60%) humidity while for M. anisopliae moderate temperature (30°C) and moderate (60%) humidity remained suitable at which maximum response was attained. Long exposure intervals and higher dose rates increased the mortality in each case. In the case of progeny development, the emergence of offspring was suppressed at moderate and low temperature for M. anisopliae and B. bassiana respectively with moderate r.h. When DE was applied in combination with the microbial insecticides, a synergistic effect was noticed in all combinations and R. dominica and S. granarius remained more susceptible as compared to O. surinamensis. The response of abiotic condition was significant for combination of DE and EPF while for DE and bacterial based insecticide it was non-significant. The results of the study divulge that all applied microbial based insecticides and DE are very effective for the control of these test insects and different abiotic conditions are responsible for affecting their efficacy. Furthermore, the combinations of these microbial insecticides with DE have a synergistic response against test insects. This study also recommends that attention should be paid to the interaction of abiotic factors with the efficacy of DE and microbial insecticides before planning IPM strategy for stored grain insect pests.