Role of PON1 L55M Gene Polymorphism in Parkinson's Disease among North Indian Population.

BACKGROUND AND OBJECTIVES: The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. MATERIALS AND METHOD: Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. RESULTS: Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. CONCLUSION: There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

A Cross-Sectional Assessment of Quantitative Epidermal Melanin and Erythema Indices among North Indians.

Background: Remarkable diversity of skin tones among Indians ranging from pale pinkish to dark brown appears to be an ideal choice for the assessment of skin pigment variation. Aim: The present study was designed to assess the variation observed in melanin and erythema indices among north Indians. Material and Methods: Skin reflectance data (n = 574) was collected from six diverse populations of north India using DermaSpectrometer (DSM II ColorMeter) followed by statistical analysis to investigate the impact of geographical location and gender on constitutive skin pigmentation. Results: The melanin index (MI) varied between 17.93 and 56.92 (Mean (M) = 35.80 ± 6.26) whereas the erythema index (EI) varied between 4.92 and 18.82 (M = 10.48 ± 2.68). MI and EI of females were found to be significantly lower than males (P < 0.001). Geographical location exhibited a significant association with MI and EI (P < 0.001). Furthermore, we have noted a positive correlation between MI and EI (P < 0.001). Conclusion: The study has refined our understanding of skin pigmentation variation among north Indians in terms of significant association with geographical location {MI: F (5,568) = 31.07, P < 0.001; EI: F (5,568) = 73.37, P < 0.001} and gender {MI: t (386) = -4.06, P < 0.001; EI: t (386) = -11.96, P < 0.001} and rendered opportunities for further studies.

Role of ACE Polymorphism in Acute Ischemic Stroke.

BACKGROUND: Stroke is one of the leading causes of death and disability in India. Angiotensin-converting enzyme (ACE) is involved in the development of hypertension, atherosclerosis, cardio, and cerebrovascular disease and is a plausible genetic candidate for stroke. The role of ACE polymorphism is still uncertain and requires further investigation. OBJECTIVE: The aim of this study was to study the role of ACE insertion/deletion polymorphism in acute ischemic stroke (AIS). MATERIALS AND METHODS: One hundred thirty AIS cases and 130 age and sex matched healthy controls were recruited. Ten milliliters venous blood was drawn and 6 mL of blood was used for routine hematological, biochemical tests. Remaining 4 mL of EDTA blood was used for DNA extraction, PCR amplification, and restriction digestion. Three genotypes (II, ID, and DD) were visualized on 3% agarose gel. Association between genotypes among stroke case was done by Chi-square test with P value <0.05 taken as significant. RESULTS: DD genotype was significantly associated with the risk of stroke with P value of 0.0001. Both the dominant and recessive models showed that the DD genotype was independently associated with an increased risk of ischemic stroke (OR = 20.732; 95% CI: 2.7241-157.7864; P value = 0.003 for the recessive model and OR = 2.848; 95% CI: 1.5127-5.3649; P value = 0.001 for dominant model). CONCLUSIONS: Our study showed a strong association between ACE polymorphism and the risk of AIS. This study paves the way for further studies to confirm the role of ACE polymorphism as genetic risk factors for AIS.

Endothelial Nitric Oxide Synthase (Glu298Asp) Polymorphism is Associated Significantly with Ischemic Stroke Presenting with Seizures and Altered Sensorium.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) is an enzymatic marker whose genetic polymorphism might predispose to acute ischemic stroke (AIS) via vascular endothelial dysfunction. It has a potential role in atherosclerosis, making it a plausible risk factor for stroke. Prior studies have failed to prove a conclusive relationship between eNOS polymorphism and AIS. OBJECTIVE: The aim of this study is to find an association between the presence of eNOS polymorphism (Glu298Asp) and the risk of developing AIS. MATERIALS AND METHODS: We recruited 307 subjects including 153 AIS cases and 154 healthy controls. The eNOS (Glu298Asp) polymorphism was identified in EDTA blood by PCR amplification of the target region followed by restriction enzyme digestion, and genotyping on Agarose gel. GG, GT and TT genotypes were obtained. Statistical analysis was done using SPSS software version 20. RESULTS: A significant association was found between the presence of TT genotype and the risk of AIS (Odd's ratio (OR): 2.43, P-value = 0.038). There was no significant association between the TT genotype and the traditional stroke risk factors. However, the TT genotype was significantly associated with the presence of altered consciousness (OR: 5.27, 95% CI: 1.59-17.04, P-value = 0.003) and with the occurrence of seizures at presentation (OR: 7.98, 95% CI: 1.99-32.09, P-value = 0.007). CONCLUSIONS: There is a significant association between the presence of eNOSpolymorphism (Glu298Asp) and the risk of AIS, and the TT genotype may predispose to a more severe initial presentation of ischemic stroke.

Sickness Status and Neural Tube Defects: A Case-Control Study in a North Indian Population.

BACKGROUND: The prevalence of neural tube defects (NTDs) in India is high in comparison to other regions in the world, with the Northern part reporting the highest prevalence. METHODS: To explore the risk factors for NTDs, a case-control study was carried out in Delhi from January 2008 to June 2011. Using multivariate logistic regression model analysis, 308 cases were compared with 580 controls and adjusted odds ratio (AOR) was calculated using SPSS version 17. RESULTS: Maternal factors that were significantly associated with increased risk of NTDs were inter-pregnancy interval (AOR = 3.175; 95% confidence interval [CI], 2.007-5.024), hyperthermia during the first trimester (AOR = 2.07; 95% CI, 1.131-3.788), maturation ill pregnancy (AOR = 1.956; 95% CI, 1.385-2.763), chronic illness (AOR = 1.648; 95% CI, 1.103-2.462), and use of antibiotics (AOR = 5.589; 95% CI, 1.789-17.455). Differences in the risk were also found between upper and lower NTD. It was observed that all of the former five variables, except for chronic illness, were associated with risk for upper NTDs (AOR = 1.532; 95% CI, 0.916-2.563). In contrast, hyperthermia before conception (and not during the first trimester) was found to be additionally associated with risk for lower NTDs (AOR = 2.782; 95% CI, 1.302-5.944). CONCLUSION: These findings highlight heterogeneity in the etiology of upper and lower NTDs. The study also highlights the risk factors that should be considered in combating the risk of NTDs. Birth Defects Research 109:1393-1399, 2017.© 2017 Wiley Periodicals, Inc.

Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India.

India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead to population-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of population makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin converting enzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone system pathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associated with various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovascular diseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribution of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respect to age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to first cousin, aged 25 to70 years were studied. ACE gene was found to be polymorphic with high frequency of heterozygote (ID) followed by II and DD genotypes. The studied population was found to be in Hardy-Weinberg equilibrium with respect to ACE I/D polymorphism (P = 0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The median level of ACE was found to be 65.96 ng/mL (48.12-86.24) which is towards lower side of the normal range. ACE levels were found to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozygote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study is low sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool.

Y chromosome haplogroup distribution in Indo-European speaking tribes of Gujarat, western India.

The present study was carried out in the Indo-European speaking tribal population groups of Southern Gujarat, India to investigate and reconstruct their paternal population structure and population histories. The role of language, ethnicity and geography in determining the observed pattern of Y haplogroup clustering in the study populations was also examined. A set of 48 bi-allelic markers on the non-recombining region of Y chromosome (NRY) were analysed in 284 males; representing nine Indo-European speaking tribal populations. The genetic structure of the populations revealed that none of these groups was overtly admixed or completely isolated. However, elevated haplogroup diversity and FST value point towards greater diversity and differentiation which suggests the possibility of early demographic expansion of the study groups. The phylogenetic analysis revealed 13 paternal lineages, of which six haplogroups: C5, H1a*, H2, J2, R1a1* and R2 accounted for a major portion of the Y chromosome diversity. The higher frequency of the six haplogroups and the pattern of clustering in the populations indicated overlapping of haplogroups with West and Central Asian populations. Other analyses undertaken on the population affiliations revealed that the Indo-European speaking populations along with the Dravidian speaking groups of southern India have an influence on the tribal groups of Gujarat. The vital role of geography in determining the distribution of Y lineages was also noticed. This implies that although language plays a vital role in determining the distribution of Y lineages, the present day linguistic affiliation of any population in India for reconstructing the demographic history of the country should be considered with caution.

Association of sociodemographic and nutritional factors with risk of neural tube defects in the North Indian population: a case-control study.

OBJECTIVE: To assess the role of sociodemographic and nutritional factors in the incidence of births affected by neural tube defects (NTD) in the North Indian population. DESIGN: Case-control study. SETTING: Government hospitals of Delhi, India. SUBJECTS: Subjects comprised 284 mothers of NTD children (cases) and 568 mothers of healthy children (controls). RESULTS: Significant differences were found between case and control mothers with respect to maternal age (P = 0·005), type of drinking water (P = 0·03) and consumption of milk (P = 0·01). Univariate and multivariate analysis suggested an association of unpasteurized milk use, low consumption of vegetables, low consumption of fruits and vegetarian dietary habits with NTD births. Further, variation in the risk factors for upper and lower NTD types was also observed, pointing towards phenotypic heterogeneity in the aetiology. CONCLUSIONS: The results of the present study suggest an increased risk of NTD infants in mothers with low consumption of vegetables, fruits and milk and having vegetarian dietary habits. So, in order to reduce these devastating birth defects in future offspring, better nutritional care should be provided to mothers by suggesting dietary modifications and augmenting additional micronutrient supplementation during the periconceptional period.

Effect of maternal Tp53 gene G412C polymorphism on neural tube defects: A study from North India.

CONTEXT: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models. AIMS: The present study is an attempt to unfold the possible role of tp53 G412C polymorphism in the incidence of neural tube defect (NTDs) in humans. SETTINGS AND DESIGN: Case-control study was carried out in government hospitals of Delhi, India. MATERIALS AND METHODS: Subjects comprised of 100 mothers of NTD children and 100 matched control mothers. Information on some environmental exposures was collected along with blood samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was carried out by PCR-RFLP method. STATISTICAL ANALYSYS: Fisher Exact or Chi square test, binary logistic model, and odds ratio (95% confidence interval) calculations were used to evaluate effect of risk factors on NTDs using SPSS v17.0. RESULTS: The 'CC' genotype of tp53 G412C showed protective effect towards the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19-1.00); however, no significant difference among overall NTD cases and controls was observed (P>0.05). Further segregation of all subjects based on 2 different communities, Hindus and Muslims, the association of 'CC' genotype of the polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33; 95% CI: 0.13-0.79). CONCLUSION: The study highlights the selective advantage provided by maternal 'CC' genotype, thereby reducing risk of cephalic NTDs, probably due to the lower apoptotic activity of the protein, however, more specifically in the presence of community-specific microenvironment.

Genomic and linguistic affinities: a study of allelic and haplotype diversity at DRD2 locus among the tribes of Gujarat, western India.

Do genetic and linguistic affinities necessarily go hand in hand? An attempt has been made in the present work to explore this dimension of population structure using three evolutionarily important TaqI sites (TaqI A, TaqI B, and TaqI D) on the dopamine receptor D2 (DRD2) locus. For the first time, DNA samples from 612 unrelated individuals belonging to 11 Indo-European-speaking tribal population groups of Gujarat, western India, have been analyzed for these three sites. All the three sites are found to be polymorphic with greater interpopulation variation seen at the TaqI B site. The average heterozygosity for the haplotype system has been found to be high in the populations under study. Most of the populations share six of the eight haplotypes pointing toward underlying genetic uniformity, which is further reaffirmed by regression analysis of heterozygosity on genetic distance. The frequency of ancestral haplotype B2D2A1 is found to range between 1.9% and 15.9%. Linkage disequilibrium between TaqI B and TaqI D sites and between TaqI B and TaqI A sites is statistically significant in all but one population. Our findings reveal strong affinities between Indo-European-speaking tribal groups of Gujarat and Dravidian-speaking tribal groups of South India, suggesting that genetic affinities may not necessarily be dependent on linguistic similarities.

Brief communication: Allelic and haplotypic structure at the DRD2 locus among five North Indian caste populations.

The dopamine D2 receptor (DRD2) gene, with its known human-specific derived alleles that can facilitate haplotype reconstruction, presents an important locus for anthropological studies. The three sites (TaqIA, TaqIB, and TaqID) of the DRD2 gene are widely studied in various world populations. However, no work has been previously published on DRD2 gene polymorphisms among North Indian populations. Thus, the present study attempts to understand the genetic structure of North Indian upper caste populations using the allele and haplotype frequencies and distribution patterns of the three TaqI sites of the DRD2 gene. Two hundred forty-six blood samples were collected from five upper caste populations of Himachal Pradesh (Brahmin, Rajput and Jat) and Delhi (Aggarwal and Sindhi), and analysis was performed using standard protocols. All three sites were found to be polymorphic in all five of the studied populations. Uniform allele frequency distribution patterns, low heterozygosity values, the sharing of five common haplotypes, and the absence of two of the eight possible haplotypes observed in this study suggest a genetic proximity among the selected populations. The results also indicate a major genetic contribution from Eurasia to North Indian upper castes, apart from the common genetic unity of Indian populations. The study also demonstrates a greater genetic inflow among North Indian caste populations than is observed among South Indian caste and tribal populations.

MTHFR C677T and factor V Leiden in recurrent pregnancy loss: a study among an endogamous group in North India.

AIM: In our study an attempt has been made to find the prevalence of genetic thrombophilia in recurrent pregnancy loss (RPL). METHODS: Methylene tetrahydrofolate reductase C677 (MTHFR C677T) and factor V Leiden (FVL) were investigated in 84 Rajput women with two or more pregnancy losses and in 80 age- and ethnicity-matched healthy controls. Restriction digestions of polymerase chain reaction product with HinfI and Mnl I were used for MTHFR C677T and FVL polymorphism detection, respectively. RESULTS: MTHFR C677T mutation was found in 9/84 patients (10.71%) and 2/80 controls (2.5%), yielding an odds ratio (OR) for RPL related to MTHFR C677T of 4.68 (95% confidence interval [CI] = 0.98-22.37; p = 0.03). FVL was found in 4/84 patients (4.76%) and none among the controls, yielding a modified OR for RPL related to FVL of 9.00 (95% CI = 0.48-169.9; p = 0.05). Both, MTHFR C677T and FVL were not found to be significantly more prevalent in patients than controls as a whole. However, MTHFR C677T showed significant association with early pregnancy loss (OR = 6.3; 95% CI = 1.22-32.85; p-value = 0.03; Bonferroni-corrected p-value = 0.04). CONCLUSIONS: Our study supports the association between MTHFR C677T and patients with early RPL among north Indian Rajputs and strengthens the notion that thrombophilia plays a role in this clinical entity.

Population severance in manipur at dopamine receptor D2 locus.

INTRODUCTION: Tibeto-Burman language-speaking Mongoloid groups of northeast India are reported to be genetically highly heterogeneous. Manipur, one of the states of this region sharing a major International border with Myanmar, is also expected to be diversified as seen by its large number of tribal and nontribal groups. A number of genomic markers, that is, autosomal, mitochondrial, and Y chromosomal ones, have been used to understand the peopling of the northeast region. AIMS: In this article, an attempt is made to understand the peopling of Manipur using three sites (Taq1A, Taq1B, and Taq1D) on the dopamine receptor D2 (DRD2) gene through allele and haplotype frequencies and their distribution patterns. METHODS: In total, 367 blood samples were collected from eight populations of which three (Meitei, Muslims, and Bamon) are nontribal groups and five (Aimol, Kabui, Paite, Kom, and Thadou) are tribal groups. RESULTS: All the three sites are polymorphic in all the studied populations with relatively lower heterozyosities indicating a genetic discontinuity between the populations of mainland India and northeast India, suggesting the unlikeliness of eastward migration of people from Africa through India. CONCLUSION: High heterogeneity and predominance of ancestral haplotype (B2D2A1) among the Meitei suggest an admixture of incoming mongoloid groups with an already existing protoastroloid element. The study also highlights the distinctiveness of Manipuri population groups with respect to DRD2 gene polymorphism.