IgG Is Higher in South Asians Than Europeans: Does Infection Contribute to Ethnic Variation In Cardiovascular Disease?
To the Editor:
Coronary heart disease (CHD) mortality is 40% higher in UK residents born in the Indian subcontinent than in the general UK population, a difference not explained by traditional cardiovascular risk factors. The burden of chronic infections has been associated with increased risk of CHD,1 and South Asians are likely to have a different lifetime exposure to infection than those of European origin. Serum gamma globulin (IgG) is a nonspecific measure of immune activation. Elevated levels have been associated with increased risk of myocardial infarction.2
We measured total IgG using quantitative enzyme linked immunosorbent assays (ELISA)3 in stored sera from 302 European and 302 South Asian participants in the Newcastle Heart Project, a stratified population sample of men and women 25 to 74 years old in Newcastle on Tyne, UK.4 The study was approved by the local ethics committee, and participants gave written informed consent. In a previous study, we measured C-reactive protein (CRP) using a highly sensitive method in a subsample of 100 South Asian participants.5 Of those included in the present study, 35 also had measurements available for CRP. IgG was log transformed, and results are presented as geometric means.
The mean age (SD) of Europeans was 54.5 years (13.1) and of South Asians 50.1 (12.1). Geometric mean IgG (95% confidence interval [CI]) was 7.4 (6.7, 8.2) g/L among Europeans and 13.5 (12.1, 15.2) g/L among all South Asians: 13.9 (11.4, 17.0) among Indians, 14.0 (11.8, 16.5) among Pakistanis, and 11.9 (9.2, 15.3) among Bangladeshis. Although levels were lowest among current smokers, IgG was higher in South Asians than in Europeans in each smoking category and in Indian, Pakistani, and Bangladeshi groups (Table). Adjusted for age, sex, and smoking status, geometric mean IgG was 75% higher (95% CI 48, 108) in South Asians.
Among 35 South Asian subjects (17 female) with information about CRP levels, there was a correlation (r=0.48, P=0.003) between log CRP and log total IgG.
Higher levels of total IgG have been reported in US blacks compared with whites,6 although the difference (30%) was much smaller than the one we report here. This and the findings we report are both consistent with the hypothesis that people with ancestral origins in tropical environments have experienced genetic selection for increased pro-inflammatory responses.7 The association between IgG and CRP in the small number of subjects with both measures available links raised IgG in this population to an established marker of CHD risk. We have also previously reported raised levels of leukocytes in Bangladeshis compared with Europeans.4
We found substantially higher levels of IgG in South Asians compared with Europeans, a difference not explained by factors known to be associated with IgG levels. This may reflect genetic differences, different exposures to infection, or ethnic differences in inflammatory processes. This finding is consistent with and could lend support to the hypothesis that the cumulative burden of infection is relevant to the excess of CHD in UK South Asians and requires confirmation from further studies.
We thank all contributors to and those acknowledged in the study reported in our Reference 4 and Dr Ananda Amarasinghe for help with study administration. We acknowledge financial support from the Barclay Trust, the British Diabetic Association, Newcastle Health Authority, the research and development directorate of the former Northern Regional Health Authority, the UK Department of Health, and the British Heart Foundation. Analysis of the serum samples was supported by a grant from the Gruss Bequest to Medical Microbiology, University of Edinburgh.
- ↵Prasad A, Zhu J, Halcox JPJ, Waclawiw MA, Epstein SE, Quyyumi AA. Predisposition to atherosclerosis by infections: role of endothelial dysfunction. Circulation. 2002; 106: 184–190.
- ↵Bhopal R, Unwin N, White M, Yallop J, Walker L, Alberti K, Harland J, Patel S, Ahmad N, Turner C, Watson W, Kulkarni A, Laker M. Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi and European origin populations: cross sectional study. BMJ. 1999; 319: 215–220.
- ↵Fischbacher C, Bhopal R, Todd T, Walker D, Bignardi G. Consider ethnic variations. http://www.bmj.com/cgi/eletters/321/7255/208. Accessed March 18, 2003.