Interleukin-6 gene-174 G/C promoter polymorphism and its association with clinical profile of patients with multiple myeloma.

AIM: In multiple myeloma (MM), the growth and survival of myeloma cells is controlled by interleukin-6 (IL-6), the plasma levels of which is controlled by a guanine/cytosine substitution occurring in position -174 of IL-6 gene promoter region. We studied the occurrence of IL-6-174 G/C polymorphism in patients of MM and correlated the presence of genotypes with serum IL-6 levels and tumor staging. METHODS: One hundred three patients with MM and 117 age- and sex-matched healthy controls were staged by International Staging System. IL-6 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were assessed by enzyme-linked immunosorbent assay. RESULTS: Frequency of GG, GC and CC genotypes did not differ significantly between cases (GG 52%, GC 40%, CC 9%) and controls. The median serum level of IL-6 was significantly higher among the GC genotype versus other genotypes (24 ng/mL, P = 0.007) as compared with the GG versus other genotypes (12 ng/mL, P = 0.001). GC was associated more with stage 3 disease (27%) than was GG (11%) or CC (22% P = 0.001). CONCLUSIONS: At position 174 of the IL-6 promoter, patients with GC genotype had higher serum levels of IL-6 and presented with more severe disease compared with patients with GG or CC genotype.

Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

Low mood and response to Levothyroxine treatment in Indian patients with subclinical hypothyroidism.

BACKGROUND AND AIM: There is considerable controversy regarding the association of subclinical hypothyrodism (SCH) and depression. We studied the association of SCH with low mood and also investigated the effects of L-thyroxine (LT4) therapy on improvement of symptoms. METHODS: Three hundred patients with SCH and 300 age and sex-matched healthy controls were studied. Serum levels of TSH, FT3, FT4 were measured by chemi-illuminescence. Hamilton Depression Rating Scale (HAM-D) was used to evaluate baseline depression in all participants and subsequently, in 133 patients who had undergone LT4 therapy for 2 months. RESULTS: The HAM-D scores were significantly higher for cases (10.0±4.7) as compared to controls (2.4±1.5). A positive correlation (r(2)=0.87, p=0.00) was found, between the Hamilton scores and serum TSH levels. No such association was seen between serum FT3, FT4 levels and HAM-D scores. Levothyroxine treatment resulted in a significant decrease in TSH levels and Hamilton scores. CONCLUSIONS: SCH is associated with low mood and there is a positive correlation between serum TSH levels and HAM-D scores. The administration of Levothyroxine therapy is associated with significant improvement in HAM-D scores. This underlines the importance of thyroid screening in cases of low mood and also asserts the role of Levothyroxine therapy.

Interleukin-6 gene -174 G/C promoter polymorphism predicts severity and outcome in acute ischemic stroke patients from north India.

BACKGROUND: A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. METHODS: One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan-Meier analysis. RESULTS: The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype (P = .03) and less severe in the GG genotype (P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10(-5); mRS P = 9 × 10(-5)), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10(-5); mRS P = 2 × 10(-4)). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan-Meier analysis. CONCLUSIONS: Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.

Lipoprotein(a), ferritin, and albumin in acute phase reaction predicts severity and mortality of acute ischemic stroke in North Indian Patients.

BACKGROUND: Inflammation plays a crucial role in the pathogenesis and prognosis of stroke. We studied the behavior of lipoprotein(a) [Lp(a)], ferritin, and albumin as acute phase reactants and their roles in the severity and mortality of stroke. METHODS: We recruited 100 consecutive patients with acute ischemic stroke and 120 controls. Blood samples were drawn on days 1 and 7 and at both 3 and 6 months. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment classification. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Prognosis at 6 months was assessed using the modified Rankin Scale, and mortality was assessed using the Kaplan-Meier analysis. Serum levels of interleukin-6 (IL-6), Lp(a), ferritin, and albumin were measured using enzyme-linked immunosorbent assay, immunoturbidimetry, and chemiluminescence commercial kits, respectively. RESULTS: Levels of IL-6, Lp(a), and ferritin were consistently higher among cases than controls (P < .0001). Serum Lp(a) levels peaked at day 7 after stroke and tapered thereafter. Albumin levels were lower than controls on admission day and increased subsequently. In our study, Lp(a) acted as an acute phase reactant while albumin acted as a negative acute phase reactant. There was no association between Trial of Org 10172 in Acute Stroke Treatment subtype and elevated serum levels of Lp(a), albumin, and ferritin. Lp(a) and ferritin were high in patients with severe stroke. Albumin was negatively correlated with stroke severity. Serum levels of Lp(a) ≥ 77 mg/dL, albumin ≤ 3.5 g/dL, and ferritin ≥ 370 ng/dL is associated with a significantly increased risk of having a poorer outcome in stroke. Serum levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL were also associated with increased mortality. CONCLUSIONS: High levels of Lp(a) and ferritin and low levels of albumin are associated with increased severity and poorer long term prognosis of stroke. Patients with admission levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL had increased mortality.

Are hsCRP Levels and LDL/HDL Ratio Better and Early Markers to Unmask Onset of Dyslipidemia and Inflammation in Asymptomatic Subclinical Hypothyroidism?

The implications of subclinical hypothyroidism (SCH) are many amongst which the most important is progression to overt hypothyroidism. Other debatable aspects are its association with cardiovascular risk, neuromuscular and psychiatric dysfunction, increased predisposition to developing metabolic syndrome and an underlying pro-inflammatory state. We aimed to study the lipid profile, lipoprotein(a) [Lp(a)] and hsCRP levels and insulin resistance in a group of patients with SCH in a referral hospital and see if any significant differences exist between them and euthyroids. This is a case-control study where the selection of controls and cases was based on the thyroid profile. Subjects were selected on their visit to clinical biochemistry lab for thyroid function tests. 33 euthyroids were taken as controls (Group I) and 38 patients comprising of subclinical hypothyroids were grouped as cases (Group II). Serum thyroid stimulating hormone (TSH) was in the range of 0.5-5.0 mIU/L for euthyroids and for subclinical hypothyroids the concentration of TSH was more than 5 mIU/L. The concentration of tri-iodothyronine (T3) and thyroxine (T4) were in normal reference range in both the groups. Individual lipid profile parameters failed to show a significant p value between cases and controls. The LDL/HDL ratio was highly significant (p value < 0.0001) and hsCRP was also statistically between the two groups (p value = 0.0054). Lp(a) and insulin resistance did not differ significantly. SCH is a common disorder that frequently progresses to overt hypothyroidism. This study underlines the importance of LDL/HDL ratio rather than measurement of individual lipid profile parameters in bringing to light the dyslipidemic state associated with SCH. Moreover the use of hsCRP to detect an underlying pro-inflammatory state in SCH can also be emphasized.