Maternal association and influence of DHFR 19 bp deletion variant predisposes foetus to anencephaly susceptibility: a family-based triad study.

OBJECTIVE: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Present study focuses on evaluating the association and influence of parental genetic effects of DHFR 19 bp deletion in the development of foetal neural tube defects (NTDs) using family-based triad approach. MATERIALS AND METHODS: The study population (n = 924) including 124 NTD case-parent trios (n = 124 × 3 = 372) and 184 healthy control-parent trios (n = 184 × 3 = 552) from Telangana, India, was genotyped for DHFR 19 bp deletion. Statistical analysis was used by SPSS and parent-of-origin effects (POE). RESULTS: Foetuses with deletion genotype (DD) were at risk of developing anencephaly (OR = 3.26, p = 0.020). Among parents, increased maternal risk of having an anencephaly foetus (OR = 2.66, p = 0.028) was observed in mothers with DD genotype. In addition, POE analysis also demonstrated higher risk of maternal transmission of the deletion allele to anencephaly foetus compared with paternal transmission (OR = 6.00, p = 0.016). Interestingly, maternal-paternal-offspring genotype incompatibility revealed maternal deletion genotype (DD) in association with paternal heterozygous deletion genotype (WD) significantly increased risk for NTDs (OR = 5.29, p = 0.013). CONCLUSIONS: This study, using family-based case-parent and control-parent triad approach, is the first to report influence of maternal transmission of DHFR 19 bp deletion in the development of anencephaly in the foetus.

Association of BCL11A genetic variant (rs11886868) with severity in ß-thalassaemia major & sickle cell anaemia.

BACKGROUND & OBJECTIVES: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including ß-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse ß-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of ß-thalassaemia major and SCA. METHODS: a total of 620 samples (420 ß-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with ß-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. ß-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of ß-thalassaemia major as well as SCA was evaluated. RESULTS: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in ß-thalassaemia major as well as SCA. INTERPRETATION & CONCLUSIONS: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of ß-thalassaemia as well as SCA.

Association of interleukin-10 gene promoter polymorphism in spontaneous abortions: a family-based triad study.

OBJECTIVE: The present study is a triad study designed to determine the co-relation of IL-10 -819C/T promoter polymorphism with the risk of spontaneous abortions. MATERIALS: A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. Fetal tissue of less than 20 weeks of gestation along with peripheral blood from all the couples was collected in this study. METHODS: A standard amplification refractory mutation system-polymerase chain reaction was carried out to determine the IL 10 genotype in all the subjects. Odd's ratio and their respective 95% confidence intervals were used to determine the strength of association between IL-10 promoter gene polymorphism and spontaneous abortions. RESULTS: The study revealed a statistically significant association of IL-10 -819C/T polymorphism between the two family groups among fetuses (p=0.0000003) and mothers (p=0.0000001). No significant difference was observed in the genotype distribution of IL-10 among fathers. CONCLUSION: An increased frequency of TT genotype and T allele was observed in spontaneously aborted fetuses and their mothers compared to respective controls. In conclusion, IL-10 C -819T gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions--a triad study.

PURPOSE: Spontaneous abortion or miscarriage is the natural death of an embryo or foetus in the early stages of prenatal development. Interleukin-10 is an anti-inflammatory cytokine, produced by human cytotrophoblasts, and defects in its production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of IL-10 -1082G/A polymorphism in spontaneous abortions by comparing foetal, maternal and paternal groups--a triad study. METHODS: A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. DNA from foetal tissue and parental blood samples were extracted, and the genotype analysis of IL-10 -1082G/A promoter polymorphism was carried out by amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. A statistical analysis was applied to test for the significance of the results. RESULTS: There was a statistically significant difference in the distribution of AA genotypes and A allele of IL-10 -1082G/A between the two family groups among foetuses (P = 0.0002) and mothers (P = 0.00005). The paternal group showed no significant difference in the genotype distribution of IL-10 between cases and controls. CONCLUSION: In conclusion, IL-10 G-1082A gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia.

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (-1082 G/A; -592 A/C and -819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 -819 C allele (P = 0·003) and -592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to -1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: -1082A with -819C (P = 0·0016); -1082G with -819C (P = 0·0018); -819C with -592C (P = 0·001); -1082A with -592C (P = 0·032); and -1082G with -592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia.

Association of serum trace elements and minerals with genetic generalized epilepsy and idiopathic intractable epilepsy.

Certain minerals and trace elements are essential for the development of healthy nervous system. Altered serum levels of these elements may lead to the development of various diseases including epilepsy. The present study was designed to evaluate the association of serum calcium, magnesium, zinc and copper in the development of genetic generalized epilepsy [GGE; erstwhile known as idiopathic generalized epilepsy (IGE)] as well as idiopathic intractable epilepsy (IIE), in which seizures persist despite treatment with at least two or three antiepileptic drugs tolerated at reasonable dosage. 200 GGE patients and equal number of healthy controls were recruited for study with their written informed consent. The patients were further divided into responders and non-responders based on their response to antiepileptic drugs. Copper and zinc levels were assayed by atomic absorption spectrophotometer whereas calcium and magnesium were analyzed by Human Star 600 fully automated biochemistry analyzer. The patients with GGE had significant low levels of calcium, magnesium and zinc (1.85 ± 0.33, 0.69 ± 0.13 mmol/L and 11.33 ± 3.32 µmol/L respectively) and the corresponding values for controls were 2.27 ± 0.22, 0.89 ± 0.15, 12.71 ± 3.24 (p < 0.05). Significant high levels of copper were found in patients as compared to controls (26.69 ± 8.79 µmol/L; 16.64 ± 3.64) (p < 0.05). Significantly decreased levels of zinc were noted in non-responders (10.38 ± 2.99) compared to responders (12.62 ± 3.30) (p < 0.05). No significant difference was observed in serum calcium, magnesium and copper levels between responders and non-responders. In conclusion, low levels of calcium, magnesium, zinc and high levels of copper were found to be associated with GGE. Further, the patients with IIE were also found to have low levels of zinc.

Association of Xmn1 -158 γG variant with severity and HbF levels in ß-thalassemia major and sickle cell anaemia.

Haemoglobinopathies including ß-thalassemia and sickle cell anaemia (SCA) are considered to be classical monogenic diseases. There is considerable clinical variability between patients inheriting identical ß-globin mutations. The reasons for this variability are not well understood. Previous studies have suggested that a variety of genetic determents influence different clinical phenotypes. The genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study 6,500 blood samples from suspected cases were analysed using HPLC, ARMS-PCR, RDB techniques. Patients with ß-thalassemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. Patients with ß-thalassemia and SCA were analysed for Xmn1 polymorphism and association between this polymorphism and severity of ß-thalassemia and SCA was evaluated. We found a significant difference in genotypic and allelic frequencies of Xmn1 polymorphism between mild and moderate and mild and severe cases. There was a significant difference in high and low percentage of HbF in CC, CT and TT bearing individuals. The TT bearing individuals were found to have a high percentage of HbF in ß-thalassemia as well as SCA. This study confirms that increased γG-globin expression associated with Xmn1 polymorphism ameliorates the clinical severity in ß-thalassemia as well as SCA in the study population.

Association of matrix metalloproteinase-7 (-181A/G) promoter polymorphism in chronic pancreatitis.

BACKGROUND & OBJECTIVES: Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 -181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. METHODS: A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (- 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). RESULTS: The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 -181GG genotype and - 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 -2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. INTERPRETATION & CONCLUSIONS: The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.

Non-Robertsonian translocation t (2;11) is associated with infertility in an oligospermic man.

Infertility is a major health problem which affects approximately 22% of married couples in reproductive age. Chromosomal defects are the most common genetic abnormalities in infertile men, with an incidence of cytogenetic abnormalities ranging from 2.1% to 15.5%. We describe here the clinical and cytogenetic studies carried out in a couple with repeated abortions. Cytogenetic analysis of the couple showed a de novo chromosomal translocation t (2;11)(p14;q21) in the male partner and a normal 46, XX karyotype in the female counterpart. Such an autosomal translocation may lead to the disruption of genes responsible for spermatogenesis or impaired synaptic complex pairing during meiosis resulting in reproductive failure.

Heterozygosity for TGF ß1 -509C/T Polymorphism is associated with risk for breast cancer in South Indian population.

Transformation growth factor ß1 is a multipotent cytokine that mediates the development, differentiation, and neoplasm of the mammary gland. TGF ß1 is known to exert both tumor suppressive and progressive effect at different stages of carcinogenesis. Several studies have shown the association of TGF ß1 expression with breast cancer markers like estrogen receptor (ER), progesterone receptor (PR), and Her2/neu. TGF ß1 expression is known to be influenced by -509C/T promoter polymorphism. Hence, the present study is aimed to evaluate the possible role of TGF ß1 -509C/T promoter polymorphism in breast cancer and its association with ER, PR, and Her2 status based on case-control study in South Indian population from Andhra Pradesh. Our study revealed a significant increase of CT genotype in breast cancer patients compared to controls (CT vs. CC: χ (2) = 6.054, P = 0.014, OR 2.005, 95 % CI 1.182-3.403). However, there was no correlation between TGF ß1 -509C/T polymorphism and other factors like age at onset, ER, PR, Her2 status, etc. Further, CT genotype was found to be associated with increased risk in advanced stages of breast cancer (CC vs. CT: OR 2.315, 95 % CI 1.143-4.688) and a border line significance with postmenopausal women (CT vs. CC: χ (2) = 3.128, P = 0.07, OR 2.095, 95 % CI 0.991-4.428).

Association of COX-2 rs20417 with aspirin resistance.

Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably stroke and myocardial infarction. However, despite the demonstrated benefit of aspirin, significant fraction of aspirin-treated patients may be resistant to the antiplatelet effects of the drug. The possible mechanisms of aspirin resistance (AR) are multifactorial. A genetic basis for AR has been suggested to exist. Therefore, the present study was taken up to investigate the role of -765G/C polymorphism (rs20417) in the cyclooxygenase-2 (COX-2) gene with AR in stroke patients. Four hundred and fifty stroke patients and four hundred and forty age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3 months post event to determine stroke outcome using Modified Rankin Scale. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. The association between the genotypes and outcome was evaluated by stepwise multiple logistic regression analysis. The COX-2 CC and GC genotype showed a significant association with bad outcome. Therefore, the carriers of C allele of COX-2 -765G/C polymorphism are more prone to AR in comparison with non-carriers. These results support a potential role of -765G/C COX-2 gene polymorphism with AR in ischemic stroke patients.

Influence of matrix metalloproteinase-1 gene -1607 (1G/2G) (rs1799750) promoter polymorphism on circulating levels of MMP-1 in chronic pancreatitis.

This study investigated the role of -1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236-3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 -1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.

Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke.

Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119-2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056-1.502); P = 0.01; OR = 1.58 (95% CI = 1.11-2.272) and P = 0.010; OR = 1.25(95% CI = 1.054-1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.

Plasma TGF-ß1, MMP-1 and MMP-3 Levels in Chronic Pancreatitis.

Chronic pancreatitis (CP) presenting clinically with upper abdominal pain, as well as exocrine and endocrine insufficiencies, is characterized by irreversible morphological and functional alterations in the pancreas. The objective of the present study is to investigate the plasma levels of transforming growth factor-ß 1 (TGF-ß1), matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysin) in CP. A total of 71 CP patients and 100 control subjects were considered for the study. Plasma levels of TGF-ß1, MMP-1 and MMP-3 were determined by enzyme-linked immunosorbent assay in patients and control subjects. The plasma levels of TGF-ß1 and MMP-1 were significantly elevated in patients compared to control group (*P = 0.0301, **P < 0.0001). However, there was no significant difference in the plasma levels of MMP-3 between patients and controls (P = 0.3756). The elevated levels of TGF-ß1 and MMP-1 may influence the inflammatory reactions by enhancing the pancreatic stellate cell activation and deposition of extracellular matrix resulting in pancreatic fibrosis. Thus, the present study highlights the role of fibrogenic cytokine marker TGF-ß1 and matrix metalloproteinases in the pathogenesis of CP.

Mosaic triple X syndrome in a female with primary amenorrhea.

BACKGROUND: Turner's syndrome is the most common chromosomal abnormality in females, affecting 1 in 2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. AIM: The aim of the study was to report a rare case of mosaic triple X syndrome in a female with primary amenorrhea. MATERIALS AND METHODS: The chromosomal analysis using GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX chromosomal constitution. Fluorescent in situ hybridization was also carried out to further confirm the observation made in the study. CONCLUSION: The physical features presented by the female could be due to the 45,XO/47,XXX mosaicism and the karyotype analysis was consistent with the diagnosis and clinical symptoms. Triple X mosaicism was confirmed with conventional and molecular cytogenetic analysis.

MMP 9 Gene Promoter Polymorphism in Gastric Cancer.

Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 -1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 -1562 C→T promoter polymorphism in the development of gastric cancer.

Role of transforming growth factor-ß1 -509 C/T promoter polymorphism in gastric cancer in south Indian population.

Gastric cancer is a multifactorial disease with the involvement of both genetic and environmental risk factors. Genetic variation in genes encoding cytokines and their receptors determine the intensity of the inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Transforming growth factor (TGF-ß) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. A hospital-based case-control study was conducted to investigate whether TGF-ß1 -509 C/T polymorphism can modify the risk of gastric cancer. Seventy endoscopically and histopathologically confirmed gastric cancer patients and 100 age and sex-matched healthy controls were enrolled in the case-control study. TGF-ß1 -509 C/T gene polymorphism was carried out by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method followed by agarose gel electrophoresis. Statistical analysis was applied to test for the significance of the results. The distribution of TGF-ß1 genotypes at -509 C/T were CC 37.14%, CT 50%, and TT 12.86% in gastric cancer patients and CC 52%, CT 42%, and TT 6% in control subjects. The allelic frequencies of C and T were 0.621 and 0.379 in gastric cancer patients and 0.73 and 0.27 in control subjects, respectively. Our study imply that T allele of TGF-ß1 -509 C/T genotypes may be a risk factor of genetic susceptibility to gastric cancer in south Indian population.

Association of tumor necrosis factor-α and matrix metalloproteinase-3 gene variants with stroke.

BACKGROUND AND PURPOSE: There is increasing evidence that the genetic variation in the genes coding for pro-inflammatory markers and matrix metalloproteinase may play an important role in the pathogenesis of various human diseases including stroke. The aim of this study was to evaluate the association of genetic variants within the genes encoding tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3), with stroke. METHODS: Five hundred and twenty-five ischemic stroke patients and 500 age- and sex-matched controls were included in this study. We analyzed +488 G/A polymorphism in TNF-α gene and -1612 5A/6A polymorphism in MMP-3 gene. The genotypes were determined by Amplification Refractory Mutation System PCR. The strength of association between genotypes and stroke was measured by the odds ratio with 95% confidence interval (CI) and chi-squared analysis. RESULTS: Allelic and genotypic frequencies of TNF-α G/A polymorphism differed significantly between patients and healthy controls (P < 0.001). A stepwise logistic regression analysis confirmed these findings (P < 0.001). Further, evaluating the association of this polymorphism with stroke subtypes, we found significant association with intracranial large artery atherosclerosis, extracranial large artery atherosclerosis, and stroke of undetermined etiology. As far as MMP-3-1612 5A/6A polymorphism is concerned, there was no significant difference in genotypic distribution and allelic frequency between the patients and healthy controls (P = 0.5 and 0.9, respectively). We tested the gene-gene interaction between TNF-α and MMP-3 genes using the logistic regression model. However, there was no evidence for a gene-gene interaction between TNF-α and MMP-3. CONCLUSION: TNF-α +488 G/A variant is an important risk factor for ischemic stroke in the South Indians from Andhra Pradesh, whereas MMP-3-1612 5A/6A polymorphism is not associated with stroke in the same population.

De novo chromosomal translocation t(3;5)(q13;q35) in an infertile man.

Chromosomal rearrangements are rare structural abnormalities that are usually associated with male infertility or sterility. We describe here the clinical and cytogenetic studies carried out in a couple with repeated abortions. Cytogenetic analysis of the male partner showed a de novo chromosomal translocation t(3;5)(q13;q35) which could be involved in the meiotic errors resulting in reproductive failure.

Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population.

Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10)-1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p<0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR=2.26; 95% C.I. (1.24-4.15), p<0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p<0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke.