Failure or severe difficulty in conceiving a child is surprisingly common, worldwide problem. Half of these cases are due to male factors with defects in sperm (1 in 15 men) being the single most common cause. Also about 60-75 % of male infertility cases are idiopathic, since the molecular mechanisms underlying the defects remain unknown. DNA methylation is crucial for spermatogenesis and high methylenetetrahydrofolate reductase (MTHFR) activity in adult testis than other organs in mouse, signifies its critical role in spermatogenesis. According to recent findings there is a correlation of epigenetic regulation of several imprinted genes with disturbed spermatogenesis and fertility. Consequently any change in the MTHFR gene sequence can modify the spermatogenesis including transmission of infertility to the carriers. The aim of the study is to analyze the distribution of the single nucleotide polymorphism C677T in the MTHFR gene in 637 North Indian infertile patients and 364 fertile North Indian men as controls by using PCR-RFLP technique and Chi Square test for statistical analysis. The average MTHFR 677CC, 677CT, 677TT genotype frequencies of total infertile men were 70.17, 24.17, 5.65 % in infertile men and 75.27, 21.7, 2.74 % in controls, respectively. The average frequency of the MTHFR 677T allele was 17.73 % in infertile men as compared to 13.59 % in controls. The statistical difference was significant. Disease risk was found 2.27-folds increased in patients who were carrying T allele. We found an association of C677T polymorphism with male infertility and that it may be a genetic risk factor for male infertility in North Indian population.

No abstract

Leptin been mainly produced by adipose tissue and cancer cells is the most studied adipokine, amongst the several cytokines. Leptin is an antiapoptotic molecule and inducer of cancer stem cells as well as activates cell proliferation. Its oncogenic, mitogenic, proinflammatory and proangiogenic actions lead to its vital roles in tumourigenesis. Two common functional DNA polymorphisms in the genes of leptin G2548A (LEP) and leptin receptor A668G (LEPR) affect the amount of circulating cytokine-type hormone leptin with risk for development of oral squamous cell carcinoma (OSCC). The present study investigated whether these LEP and LEPR gene polymorphisms are affecting risk for OSCC by comparing the genotypes of patients with controls. A total of 306 OSCC and 228 controls participated in this study. We have determined the frequency of LEP (G2548A) and LEPR (A668G) gene polymorphisms in OSCC cases and controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The incidence of leptin gene G2548A homozygous mutant AA polymorphism was significantly increased in the OSCC patients (p = 0.002, odds ratio (OR) = 2.4, 95 % confidence interval (CI) = 1.37-4.22) when compared with controls, and leptin receptor A668G homozygous mutant GG polymorphism was significantly high in the OSCC patients as compared to controls (p = 0.000, OR = 3.8, 95 % CI = 1.98-7.62). The polymorphism of homozygous mutant allele A of leptin gene and G allele of leptin receptor may be associated with increased risk for OSCC. The observations showed regular increase of supporting role of leptin in OSCC. The present study showed an association of AA genotype and A allele of LEP G2548A as well as GG genotype and G allele of LEPR A668G polymorphisms with increased risk for OSCC in north Indian patients. Moreover, the combination of both the polymorphisms may be involved in susceptibility and progression of OSCC.

The functional polymorphism A1082G in the gene (IL10) for interleukin-10 associated with risk of oral squamous cell carcinoma (OSCC). The present case-control study was to evaluate the possible association between IL10 A1082G gene and OSCC in north Indian population. Analysis of IL10 A1082G genotype in 232 OSCC cases and 221 healthy controls of comparable age, gender, smokers, tobacco chewing and alcohol consumption. IL10 A1082G status in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The frequencies of IL10 A1082G polymorphism AA, AG, GG genotypes were 29.74, 68.10 and 2.15% in OSCC cases and 57.46, 42.08 and 0.45% in healthy controls. The average frequency of G mutant allele was 36.20% in OSCC cases compared with 21.50% among the controls and this allele was associated with increased risk for OSCC cases. Heterozygous AG genotype was found statistically significant in OSCC cases than in controls (OR = 1.6, 95% CI = 1.1-2.2, P = 0.003), whereas homozygous mutant GG genotype was not found significant (OR = 4.7, 95% CI = 0.55-41.1, P = 0.2). Moreover, we found that G allele was significant in OSCC cases of tobacco chewing. The frequency of IL10 A1082G polymorphism G allele and AG genotype is associated with OSCC cases as compared with controls; this may be due to smoking and tobacco chewing. Our findings showed that in IL10 A1082G gene polymorphism AG genotype and G allele may participate in the progression of OSCC.

No abstract

Objective: To determine the frequency of mutations in exon 11 of the c-kit gene in patients with leukemia.Material and Methods: The study included 50 leukemia patients (31 with acute myeloid leukemia, 5 with acutelymphoblastic leukemia, 9 with chronic myeloid leukemia, and 5 with chronic lymphocytic leukemia) that underwentPCR-SSCP, followed by direct DNA sequencing.Results: In all, 28 of the leukemia patients were male and 22 were female, with a mean age of 31.88 years (range: 2-65years). In total, 20 mutations in 19 patients were identified, including Lys550Asn, Tyr568Ser, Ile571Thr, Thr574Pro,Gln575His, Tyr578Pro, Asp579His, His580Gln, Arg586Thr, Asn587Asp, and Arg588Met, as well as novel point mutationsat codons Ile563Lys, Val569Leu, Tyr570Ser, and Pro577Ser. Ile571Leu substitution was observed in 2 patients andTrp582Ser substitution was observed in 3 patients.Conclusion: The results suggest that mutations in exon 11 of the c-kit gene might be useful as molecular geneticmarkers for leukemia

No abstract

C-kit gene is a transmembrane tyrosine kinase that acts as type III receptor for mast cell growth factor and cellular migration, proliferation, survival of melanoblasts, haematopoietic progenitors and primordial germ cells. Apart from the scant information about the pathologies associated with loss-of-function mutations, few reports have proposed role of the c-kit gene in case of carcinogenesis. Apparently, in breast cancer the involvement of c-kit gene mutations has been considered as a rare phenomenon. Thus, we designed our study with aim to investigate the c-kit gene mutation in breast cancer, and their correlation with clinico-pathological findings. We performed mutational analysis of the c-kit gene in 58 cases of malignant breast cancer. With the aim to ascertain the variety of mutations at exon 8, 9, 11, 13, 15 and 17 of c-kit gene in breast cancer, we have done PCR-SSCP followed by DNA sequencing. In breast cancer the c-kit gene mutation rates were 3.44% (02/58) in exon 8, 5.17% (3/58) in exon 9, 5.17% (3/58) in exon 11, 3.44% (2/580 in exon 13, 3.44% (2/58) in exon 15 and 5.17% (3/58) in exon 17, respectively. The overall c-kit mutation frequency in exons 8, 9, 11, 13, 15 and 17 was determined to be 25.86% (15/58). Our study indicates to specify the role of c-kit proto-oncogene mutation in breast cancer. The result signifies that c-kit gene plays a poor role in prognosis of ductal and lobular carcinoma.