Identification of genetic polymorphisms in DNA repair xenoderma pigmentosum group D gene and its association with head and neck cancer susceptibility in rural Indian population: a hospital based case-control study from south-western Maharashtra, India

Background: Smoking and alcohol related head and neck cancer is a major concern of health risk in developing countries, such as India. In this study, we aimed to determine the frequency of polymorphisms in DNA repair gene, xeroderma pigmentosum complementation group D (XPD) at codon (cd) 156, cd199, cd320, cd751 in patients of oral cancer from South-Western Maharashtra, India and to evaluate their association with oral cancer development.Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze XPD gene polymorphisms in 320 patients with oral cancer and in 400 age and sex matched disease-free controls.Results: There was no significant difference in the genotype distribution between oral cancer patients and controls for each polymorphism (p>0.05) except XPD199. The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XPD Arg156, XPD Asn320, XPD Gln751. XPDMet199 (OR=29.44; 95% CI= (18.47-46.92); p≤0.0001) genotypes significantly increased the risk of head and neck cancer.Conclusions: This study indicates that polymorphisms in cd199 of XPD gene could play a role in modifying genetic susceptibility of individual to head and neck cancer inMaharashtra patients. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population.

Light-Induced Pupillary Responses in Alzheimer's Disease

The impact of Alzheimer's disease (AD) on the pupillary light response (PLR) is controversial, being dependent on the stage of the disease and on the experimental pupillometric protocols. The main hypothesis driving pupillometry research in AD is based on the concept that the AD-related neurodegeneration affects both the parasympathetic and the sympathetic arms of the PLR (cholinergic and noradrenergic theory), combined with additional alterations of the afferent limb, involving the melanopsin expressing retinal ganglion cells (mRGCs), subserving the PLR. Only a few studies have evaluated the value of pupillometry as a potential biomarker in AD, providing various results compatible with parasympathetic dysfunction, displaying increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum velocity of constriction (MCV) and maximum constriction acceleration (MCA) compared to controls. Decreased MCV and MCA appeared to be the most accurate of all PLR parameters allowing differentiation between AD and healthy controls while increased post-illumination pupillary response was the most consistent feature, however, these results could not be replicated by more recent studies, focusing on early and pre-clinical stages of the disease. Whether static or dynamic pupillometry yields useful biomarkers for AD screening or diagnosis remains unclear. In this review, we synopsize the current knowledge on pupillometric features in AD and other neurodegenerative diseases, and discuss potential roles of pupillometry in AD detection, diagnosis and monitoring, alone or in combination with additional biomarkers

Light-Induced Pupillary Responses in Alzheimer's Disease

FRONTIERS IN NEUROLOGY10AP

Identification of genetic polymorphisms in DNA repair xenoderma pigmentosum group D gene and its association with head and neck cancer susceptibility in rural Indian population: a hospital based case-control study from south-western Maharashtra, India

Background: Smoking and alcohol related head and neck cancer is a major concern of health risk in developing countries, such as India. In this study, we aimed to determine the frequency of polymorphisms in DNA repair gene, xeroderma pigmentosum complementation group D (XPD) at codon (cd) 156, cd199, cd320, cd751 in patients of oral cancer from South-Western Maharashtra, India and to evaluate their association with oral cancer development.Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze XPD gene polymorphisms in 320 patients with oral cancer and in 400 age and sex matched disease-free controls.Results: There was no significant difference in the genotype distribution between oral cancer patients and controls for each polymorphism (p>0.05) except XPD199. The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XPD Arg156, XPD Asn320, XPD Gln751. XPDMet199 (OR=29.44; 95% CI= (18.47-46.92); p≤0.0001) genotypes significantly increased the risk of head and neck cancer.Conclusions: This study indicates that polymorphisms in cd199 of XPD gene could play a role in modifying genetic susceptibility of individual to head and neck cancer inMaharashtra patients. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population.