Inbreeding and congenital heart diseases in a North Indian population

The study was performed in six mohallahs (colonies) of Aligarh City (North India). All six mohallahs are predominantly inhabited by Qureshi (meat sellers, a highly endogamous group) Muslims. A total of 1721 infants and children up to the age of 6 years were examined to determine the incidence of congenital heart diseases (CHD) in relation to the degree of consanguinity of the parents. Around 43% of the subjects were the offspring of consanguineous marriages including second-cousin, first-cousin-once-removed and first-cousin. A higher percentage of CUD was found in the offspring of consanguineous marriages: about 3.37% out of 741 children as compared to 1.22% in 980 offspring of non-consanguineous marriages, whereas in the first-cousin offspring, the percentage of CHD rose to 4.41%. The differences were found to be statistically significant. The present study suggests a genetic influence and also casts doubt on the applicability of a polygenic threshold model to all forms of cardiac malformation.     

Prevalent HBV genotypes and subtypes in a South Indian population.

BACKGROUND: Genotypes or genetic subtypes describe genetically related strains and have been described for viruses belonging to several different families. The eight major genotypes of hepatitis B virus (HBV) have distinct geographic distribution. Recent studies suggest possible pathogenic and therapeutic differences among HBV genotypes. OBJECTIVES: To evaluate the HBV genotypes of 85 samples by RFLP analysis and sequence the desired region to look for variations and identify the subtypes of the surface region. STUDY DESIGN: We studied 85 patients with HBV in order to identify the most prevalent genotype and subtype. Patients with HBV-related liver disease attending the Department of Gastroenterology at Owaisi Hospital and Research Centre were studied. RESULTS AND CONCLUSIONS: Genotype D1 was most prevalent. Genotyping was carried out by RFLP analysis and confirmed by sequencing. Nucleotide sequences showed significant homology (96-97%) with the other genotypes that have been reported. Subtype ayw was the most prevalent subtype within the surface region. Construction of a phylogenetic tree incorporating these isolates and other published HBV sequences showed that the isolates are derived from the same evolutionary tree. The study adds to our understanding of the genetic diversity of HBV and the geographical distribution of its subtypes, and will be useful for reconstructing the evolutionary history of HBV.     

Apolipoprotein E allele frequencies in a South African Indian female population

Coronary heart disease is common amongst South Africans of Indian (Asian) ancestry. As part of an investigation into risk factors in premenopausal and post-menopausal Indian nurses, we determined the apolipoprotein E genotype by means of restriction isotyping on 173 healthy nurses between the ages of 25–55 years. The apolipoprotein E allele frequencies on 346 chromosomes were: ε2, 1.2% (95% confidence interval 0.06-2.66); ε3, 87.6% (95% confidence interval 84.1–91.1 and ε4, 11.3% (95% confidence interval 7.94-14.60). No ε2/2 homozygotes were encountered. Our results demonstrate an extremely low frequency of the ε2 allele, a low-normal apo ε4 and a high ε3 allele frequency. It is unlikely that apolipoprotein E polymorphism contributes to the high incidence of coronary heart disease in this population.     

Inbreeding effects on fertility and sterility in southern India

The effects of consanguineous marriages on couples' fertility and sterility were explored through an interview survey of 20 626 women, chosen randomly from the rural and urban areas of the North Arcot District of Tamil Nadu State. Qualified women investigators obtained relevant information about reproductive performances of all married women resident in well defined rural and urban samples chosen randomly from North Arcot District. For each marriage, a family pedigree was drawn, extending upwards to two earlier generations on both sides of each spouse, in order to determine the existence and type of consanguinity involved. Of marriages in rural areas, 46·9% were consanguineous, and in urban areas, 29·1%. In more than 80% of the consanguineous marriages, the spouses were first cousins or more closely related. The extent of primary and secondary sterility and the level of fertility were examined in relation to each type of consanguineous marriage with the duration of the marriage and the age of the woman.

The frequency of primary sterility appeared to be lower in the consanguineous marriages compared to that in the non-consanguineous marriages. However, the differences were only marginal and only occasionally attained statistical significance. No trends were seen in the degree of consanguineous relationship, and there did not appear to be any association with the duration of marriage or the age of the woman.

The frequencies of secondary sterility did not differ significantly in consanguineous marriages in either the rural or the urban areas. No consistent associations were observed with degree of relationship. There were no specific associations in terms of the duration of marriage or the age of the woman observed in the frequencies of secondary sterility.

The mean levels of fertility were slightly raised among the consanguineous marriages and attained significance merely because of the large sample sizes involved.

These findings are discussed and compared with relevant published work. Comparisons are made difficult because of paucity of data based on community studies, and also because great differences exist in the methodology adopted by various investigators. The findings from the present study seem to show that long-term inbreeding results in only marginal or non-significant effects on fertility of inbred populations.

     

Association of mannose-binding lectin polymorphisms and HBV outcome in a South Indian population

Mannose binding lectin (MBL) is an important innate immune system pattern recognition molecule. The MBL gene polymorphisms are reported to play a crucial role in outcome of hepatitis B virus (HBV) infection. In this study, we ascertained the association of MBL genotypes with HBV outcome in a South Indian population. The MBL gene polymorphisms at codons 52, 54 and 57 of exon I, and promoter polymorphisms at −221 were typed by polymerase chain reaction-sequence specific primer in spontaneously recovered and in chronic HBV group. The allele frequency of codon 52 ‘C’ was significantly higher in chronic HBV group than in the recovered group (98.5% vs. 93.6%; P = 0.003) and codon 52 ‘T’ was significantly higher in recovered group than in the chronic group (6.4% vs. 1.5%; P = 0.003). In multivariate analysis, after adjusting for age, sex and state of origin, codon 52 ‘CC’ and ‘CT’ genotypes were significantly associated with chronicity and recovery respectively [odds ratio (OR), 0.25; 95% confidence interval (CI), 0.08–0.80, P = 0.02] in co-dominant analyzing models. This was re-affirmed in analysis performed exclusively on Tamil Nadu subjects (OR, 0.23; 95% CI, 0.06–0.93, P = 0.039). The frequency of low/none haplotype (XY/O) was significantly higher in recovered group than in chronic group (15.6% vs 7.5%) and associated with spontaneous recovery (OR, 2.28; 95% CI, 1.04–4.99, P = 0.035). Our results provide preliminary evidence that inheritance of codon 52 genotypes and XY/O haplotype associated with low MBL level substantially determine the outcome of HBV infection in a sympatrically isolated South Indian population.     

Inbreeding depression and intelligence quotient among north Indian children

This study presents the assessment of inbreeding depression on the intelligence quotient among north Indian Muslim Children of school age. The Weschler Intelligence Scale for Children (WISC-R)-74 was given to the children in both groups (50 each non-inbred and inbred of the first-cousin status), aged 6 to 11 years and from the same socio-economic status. The change of the mean follows genetic theory; however, the nature of the change in variance seems to be somewhat different.     

Promoter polymorphism of IL-18 gene in pulmonary tuberculosis in South Indian population

Interleukin-18 (IL-18) plays a vital role in both innate and acquired immunity. We analysed polymorphisms at -607(C/A) and -137(G/A) in the promoter region of IL-18 gene by allele-specific polymerase chain reaction in normal healthy subjects (n = 173) and patients with pulmonary tuberculosis (n = 165). Allele, genotype and haplotype frequencies did not differ significantly between normal healthy subjects and patients. The results suggest that the IL-18 gene promoter polymorphisms are not associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population of Dravidian descent.     

Endothelial nitric oxide gene polymorphisms,nitric oxide production and coronary artery disease risk in a South Indian population

Nitric oxide (NO) synthesized by vascular endothelial cells, is a vasodilator agent produced from endothelial NO synthase (eNOS). It has been reported that decreased bioavailability of NO plays an important role in the development and progression of atherosclerosis.Electrocardiographically proven 100 patients with acute myocardial infarction and 100 age and sex matched healthy individuals with normal coronary arteries were included for the study. The genotypes of a 27-bp insertion/deletion in intron 4 (eNOS 4b/4a) and G894T polymorphism in exon 7, were determined by PCR analysis based on the banding pattern on gel electrophoresis. The genotype frequencies were calculated following the Hardy–Weinberg law. Serum NO level was also estimated by the Griess method. NO levels in AMI patients were higher than those of the healthy subjects (median [interquartile range], (14.36[12.42–15.78]) μM compared with 11.28[10.32–11.89]) μM; p < 0.001; Mann–Whitney rank sum test, U = 285. Mutant “T” allele frequency of the eNOS-G894T polymorphism was found to be comparatively higher (0.29) in AMI patients than among the controls (0.17). The calculated Odds ratio showed that the occurrence of mutant allele “T” was 1.6 fold as frequent in cases than controls [OR = 1.6 (95%CI 0.898 to 2.833)].To conclude, in the present study, (i) NO levels were found to be increased in patients than in controls, (ii) the homozygous mutant (TT) genotype confers genetic susceptibility to coronary artery disease (iii) both the eNOS 4a/b and G894T polymorphisms were not associated with serum NO levels in a South Indian Tamil population.     

Impact of inbreeding on fertility in a pre-industrial population

Little is known about the effects of inbreeding on reproduction in modern human societies. It appears indeed that biological effects are hidden by socioeconomic factors, which are the major determinants of fertility. It has been established, in particular, that socially induced reproductive compensation tends to homogenize the number of offspring per family in a given population. Besides, in the field of evolutionary biology, a number of empirical and theoretical studies have shown that the effects of inbreeding are condition dependent. In particular, theoretical developments on the evolution of senescence predict that the deleterious effects of inbreeding should increase with age. We rely on these developments to examine the effects of inbreeding on fertility in a cohort of Canadian women born in the late 19th century. The analysis does not allow for the detection of any effect of inbreeding on the overall number of offspring of women. However, results indicate that high levels of close father inbreeding are associated with a reduction of the productivity of parents during the second half of their reproductive period, as compared with the first half. We suggest that inbreeding depression affects reproduction in modern societies through an interaction with age.     

Vaccinia reactive antibodies in a south Indian population

The prevalence of vaccinia virus antibodies was determined in both urban and rural populations in southern India. The study sample consisted of 211 adults and 52 children. The antibody titre was measured in all sera by virus neutralisation and by indirect immunofluorescence assay (IFA). A small panel of sera was tested by Western blotting. There was no significant difference in detection rates between the tests. Generally, seropositivity correlated with a previous history of vaccination. All children were negative for vaccinia antibodies. Among adults overall, 54% had neutralising antibodies whereas 60% were positive for antibodies detected by IFA, however, the prevalence of vaccinia antibody by either method was significantly higher (P < 0.001) among rural subjects than in urban subjects. This higher antibody prevalence among the rural population could be due to exposure to other indigenous orthopoxviruses, possibly buffalopox.     

A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population

Background  

Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It also exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. The aim of our study was to do a case-control association analysis of common variants in GIP in association with type 2 diabetes and related biochemical parameters.     

Inbreeding effects on human reproduction in Tamil Nadu of South India

A prospective investigation of inbreeding effects was carried out during 1969-74 on representative samples from rural and urban populations of Tamil Nadu in southern India. Altogether, 14243 pregnancy terminations were observed. Forty-seven per cent of the rural women and 29% of urban were consanguineously married; in 80% or more of these marriages the spouses were first cousins or more closely related. The differences between the consanguineous and non-consanguineous marriages were studied with respect to total foetal loss rates, neonatal, infant and perinatal and extended first-year mortality rates; in these cases the differences were quite small and unlikely to have practical importance, though some attained statistical significance. Differences for duration-specific foetal loss, sex ratio and incidence of congenital malformations were not statistically significant. When studied alternatively in terms of the regression of the incidence rate on the inbreeding coefficient, again most regression coefficients were mostly positive but did not reach the 0.05 significance level. Taking into account the background of the population studied, the methodology adopted, and the lack of significant patterns by type of parental consanguinity, the most reasonable conclusion is that the continued practices of consanguinity over several generations have narrowed the differentials of human reproduction and of its wastage among various types of marriages based on parental consanguinity.     

The shape of high fertility in a traditional Mennonite population

Background: The Wenger Mennonites, a traditional horse-and-buggy group, are one of at least 30 embedded Anabaptist religious groups in the USA.

Aim: This first study of Wenger fertility documents, explains, and compares Wenger fertility to three other Anabaptist groups: the Amish, the Hutterites, and the Old Colony Mennonites.

Subjects and methods: The 1997 Wenger church directory provides household and fertility data for 14?530 individuals. This directory was transformed into an SPSS database so that age-specific birth rates could be analysed.

Results: From 1966 to 1996, total fertility ranged from 10.68 to 8.31 for married women, and age-specific fertility rates for 20–24-year-old women never dropped below 0.500. For similar time periods, no higher rates were found in any of the comparison groups. Even so, fertility has dropped over 22% in the last 30 years, suggesting increasing regulation of fertility.

Conclusion: Wenger fertility has been very high, at least since the 1960s, and continues to be higher than the comparison groups, even though there is some evidence of fertility decline, especially in older women. This high fertility is powered by high economic and social capital, and a farming community with a strong pro-natalist ideology.     

The shape of high fertility in a traditional Mennonite population

BACKGROUND: The Wenger Mennonites, a traditional horse-and-buggy group, are one of at least 30 embedded Anabaptist religious groups in the USA. AIM: This first study of Wenger fertility documents, explains, and compares Wenger fertility to three other Anabaptist groups: the Amish, the Hutterites, and the Old Colony Mennonites. SUBJECTS AND METHODS: The 1997 Wenger church directory provides household and fertility data for 14530 individuals. This directory was transformed into an SPSS database so that age-specific birth rates could be analysed. RESULTS: From 1966 to 1996, total fertility ranged from 10.68 to 8.31 for married women, and age-specific fertility rates for 20-24-year-old women never dropped below 0.500. For similar time periods, no higher rates were found in any of the comparison groups. Even so, fertility has dropped over 22% in the last 30 years, suggesting increasing regulation of fertility. CONCLUSION: Wenger fertility has been very high, at least since the 1960s, and continues to be higher than the comparison groups, even though there is some evidence of fertility decline, especially in older women. This high fertility is powered by high economic and social capital, and a farming community with a strong pro-natalist ideology.     

Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population

The role of host genetic factors in the pathogenesis and outcome of hepatitis B virus (HBV) infection is not well known. We assessed the association of HLA and TNF (rs361525, rs1800629, rs1799724, rs1800630 and rs1799964) polymorphisms with HBV outcome in the South Indian population. Association of HLA polymorphism was analyzed in 90 individuals from each group, that is, spontaneous recovery (SR) and chronic-HBV (C-HBV) infection. The role of TNF polymorphisms was evaluated in 150 subjects with SR and 137 patients with C-HBV infection. After adjusting for age and sex, HLA-DRB1*07:01 was strongly associated with chronicity (corrected P-value (pc) <0.005, odds ratio (OR) 3.76, 95% confidence interval (CI) 1.84-7.68). The rs1800630 genotype was associated with HBV outcome in codominant (pc<0.01, OR=1.99, 95% CI 1.30-3.05) and dominant (pc<0.01, OR=2.28, 95% CI 1.35-3.84) analyzing models after adjusting for age and sex. Similarly, the rs1799964 genotype was associated with HBV outcome in codominant (pc=0.01, OR=1.57, 95% CI 1.09-2.27) and dominant (pc<0.01, OR=2.21, 95% CI 1.27-3.83) analyzing models. Haplotype analysis (rs1799964/rs1800630/rs1799724/rs1800629/rs361525) revealed that the CACGG haplotype was strongly associated with C-HBV infection (P=0.0004). Our study suggests that inheritance of HLA and TNF polymorphisms might explain the outcome of HBV infection in the South Indian population.