Huidrom Suraj Singh

DRD2 and ANKK1 Gene Polymorphisms and Alcohol Dependence: A Case–Control Study among a Mendelian Population of East Asian Ancestry

AIMS Dopamine receptors are extensively studied in association with alcohol dependence (AD), since they are thought to be the key neural substrate for alcohol and other drug-related reinforcement and reward behaviours. The present study aims to understand the role of dopamine receptors in susceptibility to AD with respect to three sites of DRD2 gene (-141C Ins/Del, TaqIB and TaqID) and TaqIA site of ANKK1 gene among Meiteis of Manipur, a Mendelian population of India. METHODS A total of 129 individuals who all met the DSM-IV criteria for AD and 286 controls were screened for four single-nucleotide polymorphisms (SNPs) -141C Ins/Del, TaqIB TaqID and TaqIA. Both AD cases and controls were unrelated up to first cousin. RESULTS Early age of onset of alcohol consumption and smoking status were significantly associated with AD. Improvement in education and occupation statuses showed decreased risk of AD. The heterozygous and mutant homozygous conditions of ANKK1 TaqIA polymorphism were found to be significantly associated with AD (odds ratio = 2.13, 95% confidential interval 1.04-4.39, P < 0.05), whereas a borderline significance of the -141C Del allele was observed (P = 0.059). Such a trend was not observed between AD and the other polymorphism, i.e., TaqIB and TaqID. CONCLUSIONS Individuals carrying the A1 allele of ANKK1 TaqIA polymorphism may be relatively more susceptible to AD. Interaction of both ANKK1 TaqIA and -141C Ins/Del polymorphism is likely to increase risk of AD phenotypes among Meiteis of Manipur, India.

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.

A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India

Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P > 0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.

Haptoglobin Polymorphism among Brahmins of Solan District Himachal Pradesh

Abstract Haptoglobin is a plasma glycoprotein that binds free hemoglobin with high affinity and prevents the loss of iron. In the present study 83 unrelated individuals from the Brahmin community of Solan District of Himachal Pradesh, were screened for haptoglobin polymorphism. Haptoglobin was found to be polymorphic in the selected population but the system was not found to be in Hardy Weinberg Equilibrium (÷2 = 10.83) due to the over representation of Hp2-2 type in the population. A very high frequency of HP*2 allele (0.97) was found in the presently studied population.

Dopamine receptor D4 (DRD4) gene polymorphism among Gaddi tribe of Himachal Pradesh.

Dopamine is one of the most important neurotransmitters in the brain. D4 receptor of dopamine shows the largest number of polymorphisms among all the dopamine receptors and is one of the most polymorphic of all the genes studied (Chang et al. 1996). DRD4 gene is reported to be associated with personality associated traits like novelty-seeking. The polymorphism in DRD4 is revealed in the variable number of imperfect 48 bp tandem repeats in exon 3, ranging from two to 11 repeat units, with over 67 different haplotype variants (Ding et al. 2002; Grady et al. 2003). In most geographical locations, the 4R allele is the most common, whereas 2R and 7R allele frequencies vary widely (Chang et al. 1996; Ding et al. 2002). The 4R and 7R repeats are the most common worldwide (Chang et al. 1996). 4R and 2R alleles are common in Indian subcontinent (Chen et al.1999). 7R is absent among most of the Indian tribes and rare among caste groups of India. (Saraswathy et al. 2013). This study is an attempt to find out the distribution of DRD4 variants among Gaddis, a transhumant population of northern India. Transhumance is seasonal and short term (for 2–4 months) micro-migration with livestock due to unfavourable change in environment.

Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and alcohol consumption in hyperhomocysteinaemia: a population-based study from northeast India.

Chronic alcohol consumption is often found to be associated with hyperhomocysteinaemia through inhibiting methionine synthase. Moreover, single nucleotide change in MTHFR C677T gene also leads to hyperhomocysteinaemia. A total of 598 unrelated individuals (case = 451; control = 147) aged 25–70 years were screened for MTHFR C677T polymorphism by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion. Plasma homocysteine (Hcy) levels were measured using chemiluminescence technique to understand the role of both alcohol consumption and 677T allele independently and in combination in the causation of hyperhomocysteinaemia. Results indicate a relatively higher frequency of 677T allele among cases. Both cases and controls show higher mean plasma Hcy levels (>25 μmol/L), however, difference was not statistically significant. Individuals carrying mutant 677T allele did not show significant difference for Hcy level in both the groups. However, caseswith mutant TT genotype presented significant increase in Hcy level. Neither 677T allele, nor alcohol consumption is found to predispose individuals to higher homocysteine levels. However, TT genotype coupled with alcohol consumption leads to significant increase risk of Hcy levels. Chronic alcohol consumption is one of the leading health risks and according to WHO (2011) it is world’s third largest risk factor for disease and disability. More than 60 disease conditions have been reported to be associated with alcohol consumption (Gmel and Rehm 2003). Alcohol consumption is often found to be associated with hyperhomocysteinaemia, i.e., elevation of

Distributions of A 1 A 2 BO and Rh blood group among Gonds and Panikas of Madhya Pradesh

Abstract The present study deals with the distribution of A1A2BO and Rh blood groups among Gonds (107) and Panikas (115) of Anuppur district and Dindori district of Madhya Pradesh. The phenotypic frequency of blood group B was found to be higher among Gonds, whereas blood group O in Panikas. The phenotypic frequency distribution of Rh (D) antigens is higher than that of Rh (d) among both of the populations. However, allelic frequency distribution of Rh*D and Rh*d was found to be more or less similar among both of the populations.

Haptoglobin polymorphism among fourteen populations of India.

Haptoglobin (HP) is a serum protein that has the capability of binding the extracorpuscular haemoglobin released during haemolysis. It plays an important role in protection of haemolytic disease by reducing the oxidative and peroxidative potential at free haemoglobin. The present study was aimed to determine the prevalence of HP polymorphism among different Indian populations, anthropologically belonging to diverse ethnicity. The polymorphism was screened among 642 unrelated individuals belonging to 14 population groups of India including both tribal and non-tribal caste groups from different geographical regions of India with distinct linguistic affiliations. An attempt is also made to understand the distribution of HP polymorphism among the studied populations. The result reveals the HP gene to be polymorphic in all the studied populations. Except the two tribal populations (Thotis of Andhra Pradesh and Patelias of Rajasthan) and one caste population (Rajput of Himachal Pradesh), all the studied populations are found to obey the Hardy-Weinberg equilibrium. The significance of the present study is elucidated with the prevalence of high mutant HP*2 allele frequency in India. Selection could be one of the most plausible explanations for this high HP frequency because of its uniformly high occurrence among all the studied populations.