Methylenetetrahydrofolate reductase gene polymorphism in coronary artery disease patients

Coronary artery disease occurs with the interact ion between environmental influences and genetic factors. Genetic susceptibility may be caused by mutations and polymorphisms in a variety of genes mainly involved in blood coagulation, metabolism of lipids, homocysteine and or iron. The most common form of genetic hyperhomocysteinemia results from the production of a thermolabile variant of methylene tetrahydrofolate reductase [MTHFR] with reduced enzymatic activity. This study was performed on ninety individuals selected with normal serum glucose, kidney, liver, and thyroid function test and lipid profile. They classified into: Group I: 27 apparently healthy persons as control group. Group II: 3 apparently healthy persons with elevated homocysteine level. Group III: 27 CAD patients with normal coronary angiography. Group IV: 33 CAD patients with abnormal coronary angiography. The following specific investigations were done for all the studied persons:- Serum homocysteine [Hcy], serum folic acid [FA] and MTHFR genotyping by PCR-RFLP

Results: In group III three patients had elevated Hey [11.1%]. There was significant elevation of Hey level in group IV compared to group I [P<0. 05].however there were insignificance differences in mean value of folic acid of the studied groups compared to each other. As regard the relation between the MTHFR polymorphisam and hey and FA levels, in group I there was significant elevation of serum Hey level in carriers of CT genotype compared to carriers of CC genotype [P<0.05]. Homocysteine level was highly elevated in patients had TT genotype in group III and group IV when compared to CC and CT genotypes and this was statistically highly significant [<0.000] in group IV, but insignificant elevation in group III Folic acid level was not differing between patients had TT genotype when compared to CC and CT genotype in all studied groups and that was statistically insignificant. When we study the severity of CAD in group IV there was insignificant elevation of serum Hey level in group of one vessel affection compared to group of two vessel and multi vessel affection, there was Significant elevation of serum Hey level in group of >/= 90% stenosis compared to group of >50-75% stenosis and 75-90% stenosis. However there was insignificant difference in serum FA between the groups compared to each other. Homozygous TT was detected in group of one vessel affection and with >90% stenosis. Carriers of TT genotypes in group of one vessel affection and in>/= 90% stenosis had highly significant elevation [P<0.000] of serum homocysteine compared to CC and CT genotypes in the same group

Conclusion: Our findings support that homozygous MTHFR TT genotype is a genetic risk factor for CAD

Leptin, osteocalcin, and bone mineral density in post-hepatitic liver cirrhosis

The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Some studies have found leptin to be a potent inhibitor of bone formation. The aim of this study is to investigate the relationship between leptin, osteocalcin and bone mineral density [BMD] in liver cirrhosis. Sixty patients with post-hepatitic liver cirrhosis were classified into three groups: group I, 20 pre-menopausal females; group II, 20 post-menopausal females; and group III, 20 males. In addition, 21 age- and sex-matched healthy subjects [seven for each group] were included as control subjects. Patients were classified according to Child-Pugh classification into grade A [n = 0], grade B [n = 38] and grade C [n = 22]. Serum osteocalcin, leptin and parathyroid hormone [PTH], in addition to liver functions test, hepatitis B surface antigen [HBsAg], anti-hepatitis C virus [HCV], serum phosphorus and calcium were measured. Bone mineral density [BMD] was measured by calcaneal ultrasound. Leptin was elevated in all groups [I, II and III] when compared with their control groups [p < 0.01, p < 0.001 and p < 0.01, respectively]. Further, it was high in female groups [I and II] compared to males [group III], [p < 0.01 each]. BMD and serum osteocalcin decreased in each group compared with the respective control [p < 0.001; p < 0.01 in group I, p < 0.05; p < 0.001 in group II and p < 0.001; p < 0.001 in group III, respectively]. In the Child-Pugh grade C group, BMD and osteocalcin were low [p < 0.001, p < 0.05, respectively], while serum leptin was elevated [p < 0.05], when compared with grade B group. Leptin correlated negatively with serum osteocalcin [r = -0.553; p < 0.001], BMD [r = -0.229; p < 0.05], albumin [r = -0.449; p < 0.001] and albumin/globulin [A/G] ratio [r = -0.661; p < 0.001], while positively correlated with both aspartate transaminase [AST] [r = 0.462; p < 0.001], and alanine transaminase [ALT] [r = 0.483; p < 0.001]. Osteocalcin negatively correlated with intact iPTH [r = -0.370, p < 0.001], while positively correlated with BMD [r = 0.418; p < 0.001], albumin [r = 0.659; p < 0.001] and A/G ratio [r = 0.444; p < 0.001]. Serum leptin was elevated in cirrhotic patients and may have a role in the pathogenesis of osteoporosis in liver cirrhosis

Apolipoprotein E 3/4 genotype as a cardiac risk marker

Atherosclerosis is a complex disease caused by both genetic and environmental factors. Apolipoprotein E polymorphism is believed to confer substantial susceptibility to coronary heart disease risk. This study was performed on sixty five males selected with normal serum glucose, kidney function, liver function and thyroid function tests. They were classified into: Group A: Apparently healthy individuals [40 subjects], with normal blood pressure and ECG. Group B: Patients with atherosclerotic coronary artery disease [CAD] diagnosed by coronary angiography [25 cases]. All the studied persons were subjected to: serum lipogram, apolipoprotems A-I, B and E concentration and apolipoprotein E genotyping. In CAD group, the mean values of serum total cholesterol triglycerides, LDL-c, TC / HDL-c ratio, LDL-c / HDL-c ratio, apolipoprotein B concentration and apo B /A-I showed significant elevation while HDL-c levels revealed significant reduction compared to apparently healthy group. In CAD group, apo E 3/3 represented 68% of cases, followed by apo E 3/4 genotype 24%, apo E 3/2 genotype 4% and the homozygous apo E 2/2 genotype 4%. In apparently healthy group, apo E 3/3 genotype represented 70%, apo E 3/4; 12.5% and apo E 3/2; 17.5% of the studied individuals. CAD patients carrying apo E 3/3 genotype, had elevations of serum triglycerides, total cholesterol, LDL-c apo B and apo B/A-I ratio in 6%, 47%. 71%, 35% and 12% of cases [respectively] while HDL-c was reduced in 65% of cases carrying this genotype compared to the levels in apparently healthy group. Average risk values of TC/HDL-c ratio were found in 65% of cases and moderate risk values in 35% of cases. High risk values of LDL-c/HDL-c ratio were found in 18% of cases and moderate values in 82% of cases. But carriers of apo E 3/4 genotype in CAD patients had elevated triglycerides, total cholesterol in 33%, 67% of cases respectively and in LDL-c, apo B and apo B/A-I ratio in 83% of cases while HDL-c and apo A-I were reduced in 83% and 67% of cases carrying this genotype respectively. High risk values of TC/HDL-c and LDL-c/HDL-c ratios were observed in 17% and 18% of cases respectively. Other genotype carriers [E3/2 and E2/2] showed no difference when compared to the levels in apparently healthy subjects. In apparently healthy group, apo E 3/4 genotype carriers had significant elevation of serum TC, TG, LDL-c, TC/HDL-c ratio, LDL-c/HDL-c ratio, apo B and apo B/A-I ratio and significant reduction of apo A-I and E concentration than apo E 3/3 genotype carriers. Carriers of E 3/4 genotype also had significant elevation of TC, LDL-c, apo B and apo B/A-I ratio and significant reduction of apo E concentration compared to those carrying apo E 3/2 genotype. 1-Apo E 3/3 is the most common genotype in both apparently healthy subjects and atherosclerotic CAD patients. If is followed by apo E 3/2, then apo E 3/4 genotypes in apparently healthy group, and followed by apo E 3/4, then apo E 3/2 and apo E 2/2 in CAD group. None of the studied individuals had either apo E 4/4 or apo E 2/4 genotypes. 2 -Apolipoprotein E 3/4 genotype carriers had elevated levels of serum total cholesterol triglycerides, LDL-c, apolipoprotein B A apo B/A-I ratio, and reduced levels of HDL-c and apo A-I.So, they are susceptible to more atherogenic lipid profile than other genotype carriers, which is considered a predisposing factor for atherosclerotic coronary artery disease. As regard TC/HDL-c and LDL-c/HDL-c ratios, most of the patients carrying apo E3/4 genotype had high and moderate risk values while patients carrying apo E 3/3 genotype had average and moderate risk values

value of lipoprotein [a], homocysteine and doppler of carotid and femoral arteries in assessment of atherosclerosis in asymptomatic cardiovascular risk patients

Atherosclerosis is a major health problem and a common cause of death in our locality. Traditional cardiovascular risk factors do not predict most future cardiovascular events. The aim of this study is to evaluate role of non traditional biochemical markers, carotid and femoral doppler in early detection of atherosclerosis in asymptomatic cardiovascular risk patients. This study was conducted on seventy two patients with various cardiovascular risk factors [22 diabetic. 15 hypertensive, 20 smokers and 15 obese], in addition to eighteen apparently healthy subjects as a control group. All patients and controls were subjected to complete history, physical examination anthropometric measurements, calculation of Framingham risk score [FS]. Measurement of serum levels of lipoproteln [a] [Lp[a]], homocysteine, insulin and C-reactive protein [CRP] as well as microalbumin in urine [UAER], in addition to lipid profile, serum glucose and calculation of insulin sensitivity [QUICKI] were done for all subjects. Also intinia-media thickness [IMT] and plaque formation were assessed in both carotid and femoral arteries using high resolution ultrasound [B mode]. According to FS patients were classified into 3 groups: group [A] 40 patients FS< 10, group [B] 25 patients FS 10-<20% and group [C] 7 patients FS >/= 20%. Also according to presence of atheroma patients were classified into two groups, group I patients without atheroma [62 patients] and group II patients with atheroma [10 patients]. Mean values of serum insulin, homocysteine, CRP, UAER and left common carotid IMT revealed significant elevation in diabetic, hypertensive, obese and smoker groups compared to controls [P<0.01 for all and P <0.05 for CRP in smoker group]. Insulin sensitivity [QUICKI] showed significant reduction in all studied groups compared to controls [P<0.01 for all]. Mean value of Lp[a] showed significant elevation in smoker group compared to controls [P<0.01], but in other groups the mean values of Lp[a] were higher but statistically insignificant. In group C [FS >/= 20%] the mean values of triglycerides, Lp[a] and IMT of both right femoral and right carotid showed significant elevation compared to group [A] FS < 10% [P<0.01 for all]. In group II [patients with atheroma] mean values of systolic blood pressure, serum insulin, triglycerides and CRP revealed significant elevation compared to patients group I [without atheroma] [P< 0.05 for all], while insulin sensitivity showed significant reduction [P<0.05]. Univariate analysis showed significant positive correlations between IMT of left carotid artery and BMI, systolic and diastolic blood pressure, cholesterol, LDL-c., triglycerides, CRP, homocysteine and FS and negative correlation with HDL-c, Also there were positive correlations between triglycerides with CRP and between Lp [a] with homocysteine. Age, waist circumference, waist/hip ratio, homocysteine, triglycerides and CRP were predictors of IMT of carotid artery: while age, CRP and triglycerides were predictors of atheroma. Non traditional biochemical markers were elevated in all cardiovascular risk groups. IMT of carotid artery correlated positively with traditional risk factors [systolic and diastolic blood pressure, BMI lipogram and FS] and negatively with HDL-c. Also it correlated positively with non traditional risk factors [CRP and homocysteine]

Role of IL-6, sIL-6R, IL-1 beta, TNF-alpha, and B2M in pathophysiology and prognosis of multiple myeloma

Cytokines control myeloma cell proliferation, differentiation, apoptosis and tumor-induced bone marrow destruction. The present study was designed to estimate the serum levels of interleukin-6 [IL-6], soluble IL-6 receptor [sIL-6R], IL-1 beta, tumor necrosis factor-alpha [TNF-alpha], and beta-2 microglobulin [beta 2M] in multiple myeloma [MM] in an attempt to elucidate their role in the disease, to study their levels in different immunologic types of MM, and to evaluate the effect of therapy on these levels. The study included 40 patients with MM, 20 newly diagnosed [group I] and 20 patients receiving treatment [group II]. Ten patients received therapy for one year [group IIb]. Patients were subclassified according to beta 2M level into [patients with beta 2M < 6 mg/L and patients with beta 2M >/= 6 mg/L]. Fifteen healthy individuals were included as controls. Samples of all patients and controls were subjected to serum protein electrophoresis, immunofixation, serum cytokines [IL-6, IL-1 beta, TNF-alpha], sIL-6R, and beta 2-microglobulin estimation. Bone marrow aspiration [for patients only] and other laboratory chemical investigations were also performed. Serum immunofixation electrophoresis revealed that out of 40 patients, 25 were IgG myeloma, 12 were IgA myeloma, one case was light chain myeloma and 2 cases had biclonal gammopathy. Serum IL-6, sIL-6R, IL-1 beta, TNF-alpha and beta 2M showed significant increase in patient groups compared to controls, with no significant difference between groups I and II in both [IgG] and [IgA] myeloma. On the other hand, IL-6, sIL-6R, and beta 2M were significantly decreased in group IIb when compared with group I and group IIa. When beta 2M level was used for subgrouping, IL-6, sIL-6R, IL-1 beta, and TNF-alpha were significantly higher in group II patients with beta 2M >/= 6 mg/L than those with beta 2M < 6 mg/L. As IL-6, sIL-6R, IL-1 beta TNF-alpha, and beta 2M were elevated in all the studied myeloma patients, they might be involved in the pathophysiology of the disease irrespective of its immunologic type. IL-6 and sIL-6R could be used in monitoring the effect of therapy in MM especially in patients with impaired renal function. In addition of being known as a good prognostic marker, beta 2M could be used to monitor the response to therapy in MM

Clinical and biochemical assessment of nutritional status in patients with chronic renal failure on regular haemodialysis

Malnutrition is common in patients with chronic renal failure [CRF] on regular haemodialysis [HD]. The aim of this study is to evaluate the extent of this problem in haemodialysis unit in Assiut University Hospitals. Sixty male patients with CRF on regular HD and 20 age and sex matched controls were enrolled in this study. All patients and controls were subjected to complete history, physical examination and estimation of anthropometric measurements [body weight [wt], body mass index [BMI], midarm circumference [MAC] and triceps skin fold [TSF]. The following investigations were done for all subjects including; peripheral hemogram, kidney functions, lipid profile, serum phosphorus [P], calcium [Ca], albumin, transferrin and ferritin, in addition to serum leptin and C-reactive protein [CRP]. The patients were classified according to uraemic score into 3 groups [A; 13 patients, B; 34 patients and C; 13 patients]. Cases were also classified, according to subjective global assessment score [SGA] of nutritional status into group A [no malnutrition, 6 patients], group B [mild to moderate malnutrition, 35 patients] and group C [severe malnutrition; 19 patients]. According to serum albumin level also patients were classified into group A [serum albumin> 40 g/L; 27 patients], group B [serum albumin 30-40 g/L; 30 patients] and group C [serum albumin< 30 g/L, 3 patients]. The mean values of wt, BMI, TSF, MAC, albumin and transferrin were significantly lower in patients than controls [P<0.001, 0.001, 0.001, 0.001, 0.01 and 0.001 respectively]. Mean levels of serum P, leptin and ferritin were significantly higher in patients than controls [P<0.001 for all]. Mean values of wt, BMI, TSF, MAC and Hb were significantly lower in group B and C than group A when patients were classified according to SGA score [P< 0.05 for B vs A and P<0. 001, 0.00!, 0.001, 0.01 and 0.05 for C vs A]. The mean values of wt, BMI, TSF, MAC, Hb and serum leptin were also significantly lower in group C than B [P<0. 001, 0.01, 0.01, 0.05 and 0.05 respectively] but mean values of ferritin were significantly higher in malnourished patients group B and C than group A [P<0.001 for each]. Mean values of TSF were significantly lower in group C than A [P<0. 05] and mean values of wt, BMI, and TSF were significantly lower in group C versus B [P<0.05 for all] when patients were classified according to uraemic score. 75% of patients had positive CRP and 20% had lymphopenia. Positive correlations were found between Hb and wt, BMI and MAC [F<0.05 for all]. Positive correlation was found between ferritin and CRP [P<0. 05] and negative correlations with BMI, TSF and MAC [P<0. 01, 0.05 and 0.05 respectively]. Malnutrition was common in patients with CRP on regular HD. Anthropometric measurements were lower in malnourished patients than well-nourished patients. Hyperleptinaemia may participate in the pathogenesis of uraemic anorexia. Inflammation may play a role in occurrence of malnutrition in CRF patients. We recommended dietary education of patients with CRF and follow up patients with anthropometric measurements. Further studies are needed to substantiate role of leptin in the development of malnutrition

Serum leptin, insulin and parathyroid hormone levels in chronic renal failure patients

Chronic renal failure patients whether they are treated with hemodialysis or on conservative treatment frequently suffer uremic anorexia and malnutrition, which is associated with increased morbidity and mortality. In this study we have measured serum leptin, serum insulin and parathyroid hormone in addition to routine kidney function tests, serum glucose, total protein, albumin, lipogram, total serum calcium and inorganic phosphorus. This study was conducted on forty five male patients with chronic renal failure and ten healthy male subjects as control group [Group I.]. According to management of chronic renal failure the patients were divided into two groups: 22 patients on conservative treatment [Group II] and 23 patients on hemodialysis [Group III]. Serum levels of both leptin and insulin revealed significant elevation in patient groups [either on conservative or on hemodialysis,] compared to controls, also in hemodialysis group compared to group on conservative treatment. Serum level of intact parathyroid hormone, also showed significant elevation in groups II and III compared to controls with no difference in comparing group Ill versus group II. Correlation study in whole patients group revealed significant negative correlations between creatinine clearance with both leptin and insulin. Also significant positive correlations were found between leptin and insulin and between leptin and intact parathyroid hormone [iPTH]. Anorexia was found in both patient groups II and III [90.9% and 91.3% respectively,]. Chronic renal failure patients have hyperleptinemia and hyperinsulinemia and there are important interactions between leptin and insulin in which each hormone may be involved in regulating the function of the other. Excess parathyroid hormone may play a role in the pathogenesis of both hyperleptinemia and hyperinsulinemia. Hyperleptinemia may be an important contributing factor for uremic anorexia

Tumor necrosis factor alpha, interleukin-10 and nitric oxide in patients with type 1 diabetes mellitus and their association with glycemic control an dsome complications of the disease

Type-1 diabetes mellitus is a disease that results from autoimmune destruction of insulin producing beta-cells. The autoimmune response against beta-cells is believed to result from a disorder of immune regulation. According to this concept tumor necrosis factor alpha [TNF-alpha], interleukin-10 [IL-10], nitric oxide [NO], urinary albumin excretion rate [UAER] and HbAIc in addition to serum glucose, kidney and liver function tests as well as lipogram were studied in sixty eight type-1 diabetic patients. Twelve healthy subjects were included as a control group According to disease duration patients were classified into three groups: group I [30 cases] patients with disease duration less than 5 years, group II [22 cases] patients with disease duration 5-10 years and group III [16 cases] patients with disease duration > 10 years. Also patients were classified according to UAER into 3 groups: group A [30 cases] normoalbuminuric patients UAER < 20 micro g/min. group B [35 cases] microalbuminuric patients UAER 20-200 micro g/min. group C [3 cases] macroalbuminuric patients UAER > 200 micro g/min. According to HbAIc levels, patients were classified into controlled group [HbALc < 6%] 20 patients and uncontrolled group [HbAIc > 6%] 48 patients. In whole patients group mean values of HbAIc, TNF-alpha and UAER showed significant elevations compared to controls [P <0.001, 0.001 and 0.05 respectively], while IL-10 revealed significant reduction. [P < 0.001]: NO mean value showed statistically insignificant elevation. Mean values of HbAIc in groups I, II, III, A, B revealed significant elevations compared to controls [P < 0.001 for all] also in group III versus group I [P < 0.05] and in group B versus A [P<0.05]. TNF-alpha showed significant elevation in groups I, II, III in comparison with controls [P < 0.001 for all]. While mean value of IL-10 showed significant reduction in groups I, III compared to controls [P < 0.01, P < 0.001 respectively] also in group III versus group I, II [P < 0.01 for both]. NO and UAER showed significant elevations in group III compared to controls [P < 0.05 and P < 0.01 respectively]. NO levels showed significant elevation in groups I and III compared to group II [P < 0.05 for both]. UAER in group III revealed significant elevation versus groups I and ii [P < 0.01, P < 0.001 respectively]. In normoalbuminuric and microalbuminuric groups [A, B] TNF-alpha showed significant elevation compared to controls [P < 0.001 for both]. IL-10 mean value showed significant reduction in groups A and B compared to controls [P < 0.001 for both]. NO levels revealed no significant differences. In uncontrolled group, level of IL-10 was significantly low, while UAER was significantly high [p < 0.05 for both]. TNF-alpha and NO showed no signifigant difference between controlled and uncontrolled groups. Positive correlations were found between TNF-alpha and serum glucose and HbAIc, also negative correlations were found between IL-10 and serum glucose, HBAIc, cholesterol, triglycerides and LDL-c. NO showed positive correlation with UAER level. From this study we concluded that increased TNF-a [proinflammatory cytokine of Th1] and decreased IL-10 levels [type 2 cytokine of Th2] may play a role in the pathogenesis of type-1 diabetes mellitus. TNF-alpha and IL-10 may be a predictor of glycemic control. Increased NO level may play a role in the pathogenesis and complications of diabetes

Assessment of total plasma homocysteine and nitric oxide levels as a risk factors in coronary heart disease

This study was performed on 40 patients suffering from Coronary heart disease [CHD] and 20 primary asymptomatic hyperlipidemia subjects compared with 20 age and sex matched healthy persons as a control group [group I]. Patients were classified into three groups: Group III: Twenty patients with acute myocardial infarction [AMI]. Group II: Twenty patients [6 with stable angina [group III[a]], and 14 with unstable angina [group III[b]] Group IV: Twenty patients with primary hyperlipidemia, without clinical and ECG evidences of ischaemic heart disease [IHD]. All patients and control groups were subjected to clinical examination, ECG: serum glucose level, Kidney, liver function tests, lipogram, CK, CK-MB and C-reactive protein, nitric oxide, [NO] and Total plasma homocysteine [tHcy] Serum total cholesterol and LDL-c levels showed statistically significant elevation in groups II, III and IV when compared with the control group. Also, serum CH, LDL-c and Triglyceride [TG] showed highly significant elevation in group IV when compared with group II and III while 9 TG was signficantly elevated only in group III compared with control Serum HDL-c revealed statistically significant reduction in all patient groups when compared to the control group, but no significant difference was observed on comparing different patient groups together. CK, CK-MB and CRP levels revealed highly significant elevation in group II and group III[b], and group IV when compared with the control group. No significance difference was observed on comparing group III[a] with the control group. Also the same parameters showed significant elevation in group II when compared with groups III[a] III[b] and IV. Also there was highly significant elevation in group III[b] when compared with group IV. But no significant difference was observed on comparing group III[a] with group IV. Serum nitric oxide [NO] revealed highly significant elevations in groups III[a], III[b] and IV when compared with the control group, while no significant difference was observed between group II and the control group. Serum NO level showed no significant difference in other patient groups when compared with each other. Homocysteine showed highly significant elevation in all patient groups when compared with the control group. In group II plasma tHcy levels showed significant elevation when compared with groups III[a],III[b] and IV. Moreover patients in group III[b] showed significant elevation when compared to group IV. Hyperhomocysteinemia is found in most of the patients with CHD and in cases of primary hyperlipidemia. So tHcy can be used as a risk factor for prediction of CHD. Also it is related to severity of CHD as it showed the highest sensitivity in AMI

Plasma nitric oxide, endothelin-1 and renin in children with acute renal parenchymal hypertension

Nitric oxide [NO], Endothetin-1 [FT-1] and plasma remin activity [PRA] in addition to complement component [C3], routine kidney function tests and peripheral hemogram, were studied in twenty four infants and children with acute renal parenchyma] hypertension [18 cases with post streptococcal glomerulonephritis and 6 cases with nephritis due to other causes diagnosed by renal biopsy]. Results were compared with those of 24 age and sex matched healthy controls. In patients group, both serum urea and creatinine levels revealed highly significant elevation compared to controls [p<0.001 for both], while glomerular filtration rate and C3 showed highly significant reduction compared to controls [p<0.001 for both]. Mean values of NO. FT-1 and PRA showed highly significant elevation [p<0.001 for all] in patients group compared to controls. No significant difference were found in biochemical tests studied in patients with posts-streptococcal in comparison to patients with nephritis due to other causes except for C[3] which reveated significant reduction in post-streptococcal glomerulonephritis compared to patients group with nephritis