Reply to Comment: Evaluation of the Association of Omentin 1 rs2274907 A > T and rs2274908 G > A Gene Polymorphisms with Coronary Artery Disease in Indian Population: A Case-Control Study.

Coronary artery disease (CAD) is a major cause of death all over the world. CAD is caused by atherosclerosis which is induced by the interaction of genetic factors and environmental factors. Genome-wide association studies have revealed the association of certain gene polymorphisms with susceptibility to CAD. Omentin 1 is an adipokine secreted by the visceral adipose tissues and has been reported to have anti-inflammatory, cardioprotective, and enhances insulin sensitivity. In this study, we examined the role of omentin-1 common single nucleotide polymorphisms (SNPs) (rs2274907 A > T and rs2274908 G > A) in CAD. We conclude that the AT genotype and the T allele of the rs2274907 A > T is associated with Cad in the south Indian population. Our results indicated that the rs2274907 SNP may be associated with CAD in this population. This finding needs further validation in well-designed and large-sample size studies before being introduced in clinical settings.

LDLR Gene Polymorphisms (rs5925 and rs1529729) Are Associated with Susceptibility to Coronary Artery Disease in a South Indian Population.

Cardiovascular diseases (CVD) are a major cause of death in India and worldwide. Atherosclerosis is caused by the interaction of environmental and genetic factors. Hypercholesterolemia is an example of a classical risk factor for CVD. The low-density lipoprotein receptor (LDLR) is one of the regulating mechanisms the liver uses for cholesterol homeostasis. Gene variations in the LDLR have been reported to cause hypercholesterolemia and consequently CVD. We investigated the association of polymorphisms in the LDLR (rs5925 and rs1529729) with coronary artery disease (CAD) in 200 coronary artery disease patients and 200 matched healthy controls using allele-specific PCR (AS-PCR). The results indicated that the CT genotype of the rs1529729 polymorphism was associated a decreased susceptibility to CAD with an odds ratio (OR) = 0.42 (95% confidence interval (CI), 0.23-0.77), risk ratio (RR) = 0.59 (0.39-0.89), P = 0.0047. The TT genotype of the rs1529729 polymorphism was also associated with decreased susceptibility to CAD with an OR = 0.19 (95% CI, 0.076-0.47), RR = 0.57 (0.47-0.69), P = 0.0003. The GA genotype of the rs5925 polymorphism was associated with decreased susceptibility to CAD with an OR = 0.45 (95% CI, 0.27-0.75), RR = 0.65 (0.47-0.88), P = 0.002. We concluded that the CT and TT genotypes of the rs1529729 polymorphism and the GA genotype of the rs5925 polymorphism are probably associated with decreased susceptibility to CAD. The simplicity of AS-PCR makes it particularly suitable for the rapid, large-scale screening of gene variabilities in the LDLR. AS-PCR could provide significant benefits in clinical applications with its ability to amplify a lower quantity of samples in a cost-saving manner. Nevertheless, these findings need to be validated in well-designed studies with larger sample sizes and in different populations.

Evaluation of the Association of Omentin 1 rs2274907 A>T and rs2274908 G>A Gene Polymorphisms with Coronary Artery Disease in Indian Population: A Case Control Study.

Coronary artery disease (CAD) is a major cause of death all over the world. CAD is caused by atherosclerosis which is induced by the interaction of genetic factors and environmental factors. Traditional environmental risk factors include hyperlipidemia, diabetes mellitus, lack of exercise, obesity, poor diet and others. Genome-wide association studies have revealed the association of certain gene polymorphisms with susceptibility to CAD. Omentin 1 is an adipokine secreted by the visceral adipose tissues and has been reported to have anti-inflammatory, cardioprotective, and enhances insulin sensitivity. In this study, we examined the role of omentin-1 common single nucleotide polymorphisms (SNPs) (rs2274907 A>T and rs2274908 G>A) in CAD. We genotyped 100 CAD patients and 100 matched healthy controls from the south Indian population using an amplification refractory mutation system (ARMS-PCR) and allele-specific PCR (AS-PCR). Our result indicated the rs2274908 G>A is not associated with CAD. Results showed that there was a significant difference in rs2274907 A>T genotype distribution between controls and CAD cases (P-value < 0.05). Results indicated that the AT genotype of the rs2274907 is associated with CAD with OR = 3.0 (95% confidence interval (CI), 1.64 to 5.49), 1.65 (1.27 to 2.163), P = 0.002. The T allele of the rs2274907 was also associated with CAD with OR = 1.82 (95% CI, 1.193 to 2.80), 1.37 (1.08 to 1.74), P = 0.005. Rs2274907 genotype distribution was also correlated with serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), hypertension and diabetes. We conclude that the AT genotype and the T allele of the rs2274907 A>T is associated with Cad in the south Indian population. Further studies on the effect of the rs2274907 A>T on omentin-1 function are recommended, and future well-designed studies with larger sample sizes and in different populations are required to validate our findings.

Incidence of MicroR-4513C/T Gene Variability in Coronary Artery Disease - A Case-Control Study.

BACKGROUND: Genetic variants in pre-microRNA genes or the 3'UTR of miRNA target genes could influence miRNA-mediated regulation of gene expression and thus contribute to the susceptibility and prognosis of human diseases. Several studies have investigated the association of genetic variants in the seed region of miRNAs with cardiometabolic phenotypes .Therefore the aim of study was to investigate the potential association of miR-4513 rs2168518 C>T gene variability with the risk of developing CAD and its association with different cardiometabolic phenotypes in an Indian cohort to stratify CAD burden in the general population. METHODS: The study was conducted on 100 clinically confirmed CAD patients and 100 healthy individuals. Genotyping of MicroR-4513 rs2168518C>T gene variability was performed using Amplification refractory mutation system PCR method. RESULTS: A significant difference was observed in the genotype distribution among CAD cases and healthy controls. The frequencies of three genotypes CC, CT, TT in CAD patient and healthy controls were 5%, 77%, 18%, and 28%, 45% and 27% respectively. A multivariate analysis showed that miR- 4513 rs2168518 polymorphism is associated with an increased susceptibility to CAD in codominant inheritance model for variant CC vs. CT OR 9.58 CI (3.45-26.57), RR 2.3(1.75-3.02), P=0.001. Results also indicate a potential dominant effect of miR-4513 rs2168518 C/T polymorphism on susceptibility of CAD in dominant inheritance model for variant CC vs. (CT+TT) OR 7.38 (2.71-20.07), RR 1.96 (1.56-2.46), P=0.001. In allelic comparison, T allele weakly increased risk of CAD compared to C allele (OR=1.50, 95% CI (1.09-2.26) RR 1.15 (0.94-1.39) P=0.044. CONCLUSION: It is concluded that CT genotype and T allele of microR-4513 rs2168518 is strongly associated with increased susceptibility to CAD. Furthers studies with larger sample sizes are necessary to confirm this result.

LDLR rs688 TT Genotype and T Allele Are Associated with Increased Susceptibility to Coronary Artery Disease-A Case-Control Study.

PURPOSE: The low-density lipoprotein receptor is responsible for the binding and uptake of plasma LDL particles and plays a critical role in maintaining cellular cholesterol homeostasis. LDLR gene SNP rs688 has been reported to be associated with increased plasma total and LDL cholesterol in several populations and can lead to elevated plasma LDL levels, resulting in an increased risk for atherosclerosis and coronary artery disease. This study aimed to explore genetic LDLR variant rs688 for its potential roles in coronary artery disease. METHODOLOGY: This study recruited 200 coronary artery disease patients and 200 healthy individuals. Genotyping of LDLR-rs688C > T gene variations was performed using the allele specific PCR method. Correlation of LDLR-rs688C > T gene variants with different clinicopathological features of coronary artery disease patients was performed. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the correlation of this microRNA polymorphism with coronary artery disease risk. RESULTS: A significant difference was observed in genotype distribution among the coronary artery disease and matched healthy controls (p = 0.003). The frequencies of all three genotypes CC, CT, TT reported in the patient samples were 14%, 65% and 21% and in the healthy controls samples were 18%, 73% and 9%, respectively. The increased risk of developing CAD in Indian patients was found to be associated with LDLR rs688 TT genotype (OR = 3.0, 95% CI, 1.43 × 6.2; p = 0.003) RR 1.87 (1.20⁻2.91) p = 0.0037) and also the increased risk of developing CAD was reported to be associated with LDLR rs688 T allele (OR = 0.74, 95% CI, 1.57⁻0.97; p = 0.03) RR 0.85 (0.73⁻0.99) p = 0.03) compared to the C allele. Therefore, it was observed that more than a 3.0- and 0.74-fold increase risk of developing CAD was associated with TT genotype and T allele in Indian coronary artery disease patients. CONCLUSION: The findings indicated that LDLR rs688 TT genotype and T allele are associated with an increased susceptibility to coronary artery disease patients. LDLR-rs688C > T gene variation can be used as a predisposing genetic marker for coronary artery disease. Further studies with larger sample sizes are necessary to confirm our findings.

Genetic affinities of the Siddis of South India: an emigrant population of East Africa.

Historical records indicate that the Portuguese brought the African Siddis to Goa, India, as slaves about 500 years ago. Subsequently, the Siddis moved into the interior regions of the state of Karnataka, India, and have remained there ever since. Over time the Siddis have experienced considerable cultural changes because of their proximity to neighboring population groups. To understand the biological consequences of these changes, we studied the Siddis to determine the extent of genetic variation and the contributions from the African, European, and Indian ancestral populations. In the present study we typed the Siddis for 20 polymorphic serological, red cell, and Alu insertion-deletion loci. The overall pattern of phenotype (and genotype) distribution is in accordance with Hardy-Weinberg expectations. Considering the ethnohistorical records and the availability of secondary-source genetic data, we used two data sets in the analysis: one comprising eight serological and red cell enzyme markers with eight population groups and another comprising six Alu insertion-deletion markers with seven tribal groups of South India. The dendrograms generated from these two data sets on the basis of genetic distance analysis between the selected populations of African, European, and Indian descent reveals that the Siddis are closer to the Africans than they are to the South Indian populations. Genetic admixture analysis using a dihybrid model (19 loci) and a trihybrid model (10 loci and 8 loci) shows that the predominant influence comes from the Africans, a lesser contribution from the South Indians, and a slight contribution from the Portuguese. Thus the original composition of the African genes among the Siddis has been diluted to some extent by the contribution from southern Indian population groups. There is no nonrandom association of alleles among a set of 10 genetic marker systems considered in the present study. The demonstration of genetic homogeneity of the Siddis, despite their admixed origin, suggests the utility of this population for genetic and epidemiological studies.

Genetic variation and structure of the people of Uttarakhand, central Himalayas, India.

The Indian Himalayas, being semi-isolated geographically, provide ideal conditions for population genetics investigations. The main aim of this study is to genetically characterize and analyze the genetic structure of the people of Uttarakhand, a newly created North Indian hill state in the Central Himalayas, using original phenotype and allele-frequency data on a battery of seven red cell enzyme polymorphisms. For this analysis, blood samples were collected from 3,222 unrelated subjects belonging to various endogamous caste populations (Brahmin, Rajput, and Shilpkar) and tribal Bhotia inhabiting seven different districts in the Garhwal (northern) and Kumaon (southern) regions of Uttarakhand. Hemolysates were typed for isozymes of ESD, PGM1, ADA, AK1, GLO1, ACP1, and GPI using standard electrophoretic techniques. The genetic structure of these regional caste and tribal population groups was investigated with the help of different statistical measures. The present biochemical marker results show that the overall genetic constitution of the different populations of Uttarakhand is rather heterogeneous but similar to that of various caste and tribal populations of the neighboring hill state of Himachal Pradesh, situated on Uttarakhand's western border. The extent of genic differentiation observed in different contemporary populations of Garhwal was twice as high as that of Kumaon. Interestingly, in genetic distance dendrograms of both the regions and of all of Uttarakhand, all the Shilpkar groups are differentiated from the remaining groups of Brahmin, Rajput, and Bhotia. The genetic constitution of the Shilpkar (a scheduled caste population of Uttarakhand) and to a lesser extent that of the Bhotia (a scheduled tribe population of Uttarakhand) are rather different from both the Brahmin and Rajput high-caste populations, which tend to show genetic similarities between them. These observations are corroborated by the known ethnohistory of different populations of Uttarakhand.

Variability of genetic markers in Himachal Pradesh, India: variation among the subpopulations.

The genetic composition of one tribal and two nontribal populations of the Chamba District, Himachal Pradesh, India, was studied by phenotype analyses of 25 genetic markers (9 blood groups, 13 red cell enzymes, and 3 serum proteins). Furthermore, the genetic structure of 11 populations from 3 districts, Chamba, Kangra, and Kinnaur of Himachal Pradesh, was also analyzed using data from 20 loci (57 alleles). Nine genetic systems (ABO, Rh, FY, P, PGM, ACP, AK, PGD, and HP) showed highly significant heterogeneity in the five populations of Kinnaur District, whereas among the six populations from Chamba and Kangra districts the genetic variation was low. The FIS value at each locus for the five populations of Kinnaur District and the six populations from Chambra and Kangra districts was consistently higher than the FST estimates, suggesting that the population structure of both regions is influenced by local random inbreeding. Although the role of selection in local genetic differentiation cannot be ruled out, the present analyses indicate that local differentiation is mainly affected by geographic proximity, random inbreeding, and admixture.

Polymorphic protein expression (profile) in numigall.

Ten protein and enzyme polymorphic systems, viz. haemoglobin, albumin, transferrin, adenosine deaminase, adenylate kinase phosphoglucomutase, esterase-D, glyoxalase, alkaline phosphatase and amylase were studied in numigall (guinea fowl x chicken hybrids) to assess structural gene expression and regulatory gene divergence between the parental species. The investigation revealed presence of both the maternal and paternal electrophoretic components in case of adenosine deaminase, alkaline phosphatase, amylase, albumin and transferrin although no clear differences could be identified for haemoglobin and glyoxalase. Esterase-D and adenylate kinase phenotypes showed a dominance of the chicken type.

Genetic epidemiology of non-insulin-dependent diabetes mellitus in north India: preliminary analyses of some genetic markers in Punjabis.

Studies on monozygotic (MZ) twins and admixed populations show that the predisposition to non-insulin-dependent diabetes mellitus has a large genetic component. We have examined the distribution of some genetic polymorphisms (ABO, GLO, ESD, AK, ACPA, and GPI) in control and diabetic Punjabis from north India. The distribution of various genetic markers indicate that the differences between the control and diabetic samples are statistically not significant. Moreover, a contingency chi-square analysis over all loci suggests nonsignificant genetic differentiation (p = 0.50) between the Punjabi samples.

Serogenetic variation in four caste populations of Haryana, India.

The phenotypes and gene frequencies of 3 blood groups, 7 red-cell enzymes and a serum protein were studied in 4 caste population groups of Haryana, North India. The results indicate that the distribution of these blood markers is rather homogeneous in the 4 groups and generally resembles that observed in various populations from neighbouring North Indian states.

Erythrocyte enzyme polymorphisms in the Kamboh caste of Patiala, Punjab.

Data are presented on six erythrocyte enzyme polymorphisms (ADA, GLO I, EsD, AK, AP, GPI) in the Kamboh, a scheduled caste inhabiting the Patiala district of the Indian state of Punjab. With their high ADA2 (18.5%), Pa (42.5%) and GPI3 (5.3%) and a rather low GLO1 (18.8%) frequencies, the Kamboh differ from all other populations of Punjab.

Biochemical variation in the Sunni Muslims of Pulwama district, Jammu and Kashmir.

Baseline data are presented on phenotype and gene frequency distributions of nine red-cell enzyme systems (ADA, AK, EsD, GLO I, PGM1, AP, GPI, PGM2, SOD) in the Sunni Muslims of Kashmir valley in the northernmost Indian border state of Jammu and Kashmir.

Electrophoretic variants of red cell phosphoglucose isomerase in some caste populations of Punjab.

Hemolysates from a total of 640 blood samples from seven endogamous caste groups of the Patiala and Faridkot districts of Punjab, North-West India, were subjected to horizontal starch gel electrophoresis to study the phosphoglucose isomerase (PGI) types. In addition to the usual pattern PGI 1, the only rare phenotype encountered in the present material was PGI 3-1, present in four out of the seven groups investigated. Examination of the available data from Punjab suggests that apparently rare PGI types other than PGI 3-1 are lacking in populations studied.

Genetic variation of esterase D (EsD) polymorphism in Indian populations.

Data are presented on the phenotypes and gene frequencies of esterase D (EsD) polymorphism in various endogamous caste groups of Patiala and Faridkot districts of Punjab, north-west India. The frequency of the EsD2 allele in these groups varies from a minimum of 0.157 in Khatris to a maximum of 0.253 in Ramdasia Sikhs, a range quite typical of the north Indian populations. Examination of the available data on esterase D system in indigenous populations demonstrates the existence of a north-south cline in the distribution of the EsD2 allele in India.

Population genetics of glyoxalase I (GLO) polymorphism in India.

Phenotype and gene frequency data are presented on the glyoxalase I (GLO) polymorphism in seven endogamous caste groups: Jat Sikh, Ramdasia Sikh, Ramgarhia Sikh, Khatri, Brahmin and Bania of Patiala district, and Jat Sikh of Faridkot district of Punjab, North-West India. Apparently, there is considerable heterogeneity in the frequency distribution of the GLO1 gene that varies from 0.168 in Bania to 0.287 in Brahmin. However, these differences are not statistically significant, and the overall GLO1 frequency in Punjab is well within the North Indian range.

Genetic studies of Pangwalas, Transhumant and Settled Gaddis. 4. Colour blindness, mid-phalangeal hair, ear lobe attachment and behavioural traits.

Frequency distributions of colour blindness, midphalangeal hair, ear lobe attachment, hand clasping, arm folding, leg folding and handedness are reported for different population groups from Himachal Pradesh, North India, namely Pangwalas, Transhumant Gaddis (Brahmans, Rajputs and Scheduled Castes) and Settled Gaddis (Brahmans, Rajputs and Schedules Castes). An attempt has been made to compare the results of the present study within and between these groups as well as with the results of other reports from different population groups of India and Asia.

Genetic polymorphism of erythrocyte acid phosphatase in Indian populations.

The polymorphism of erythrocyte acid phosphatase has been investigated in seven endogamous caste groups of Patiala and Faridkot districts of Punjab in north-west India. The frequency of the Pa allele in these groups varies from 26.8 to 38.3%, but there is no evidence for any significant heterogeneity in the total sample. The Pc allele is present in some of the groups, though in non-polymorphic proportions. Furthermore, the distribution of this polymorphism in Indian populations has been examined using gene frequency data available in the literature. The present study shows that while no clinal component is discernible in the distribution of this red cell enzyme in India, the populations of north India stand out with comparatively high Pa and Pc frequencies, and in almost all regions the incidence of these two alleles is higher in the non-tribals as compared to the tribals. The possible causes of this heterogeneity are discussed.