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ORIGINAL ARTICLE Table of Contents   
Year : 2020  |  Volume : 14  |  Issue : 1  |  Page : 9-12
Lewis blood group phenotype vis-a-vis biochemical and physiological parameters of coronary artery disease: A study in North Indian population

1 Department of Transfusion Medicine, Yashoda Hospitals, Secunderabad, Telangana, India
2 Department of Transfusion Medicine, PGIMER, Chandigarh, India
3 Cardiology, PGIMER, Chandigarh, India

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Date of Submission25-Jan-2019
Date of Acceptance02-Feb-2020
Date of Web Publication24-Jul-2020


Background: Many studies have proposed the lack of Lewis antigen as a marker for coronary artery disease (CAD); on the contrary, some of the studies found no association in this regard. This study aims to assess the association of the expression of Lewis antigen as an independent risk factor for CAD separately in males and females.
Materials and Methods: In this cross-sectional observational study, patients with angiographically proven CAD were taken as test group, and angiographically, negative patients were included as a control group. The individuals were examined for established CAD risk factor and Lewis antigen expression on red cell. Red cell Lewis phenotyping was done using microcolumn gel agglutination technology. Statistical tests were applied to see the association between lack of Lewis antigen expression and CAD.
Results: Of these 232 patients included in the study, 161 patients had more than 50% luminal stenosis in a major epicardial artery on coronary angiography (Test Group), and 71 were normal on angiography (Control Group). When males and females were considered together, there was an increased frequency of Lewis-negative phenotype among the angiography-positive group (26.7%) as compared to angiography normal control group (16.9 %), though was not statistically significant (P = 0.19). When males and females were segregated in multivariate analysis, Le (a-b-) females had a higher incidence of CAD (P = 0.03) with the odds ratio of 4.97, though an association was not found significant in males (P = 0.71).
Conclusion: The association between Lewis phenotypes and CAD was not significant in males and in among the overall study population, but this association was statistically significant in females. Further studies based on a larger sample size may substantiate as well as delineate the possible hypotheses.

Keywords: Coronary artery disease, Lewis blood group and coronary artery disease, Lewis-negative phenotype

How to cite this article:
Natarajan R, Dhawan HK, Choudhury S, Vijayvergiya R, Marwaha N. Lewis blood group phenotype vis-a-vis biochemical and physiological parameters of coronary artery disease: A study in North Indian population. Asian J Transfus Sci 2020;14:9-12

How to cite this URL:
Natarajan R, Dhawan HK, Choudhury S, Vijayvergiya R, Marwaha N. Lewis blood group phenotype vis-a-vis biochemical and physiological parameters of coronary artery disease: A study in North Indian population. Asian J Transfus Sci [serial online] 2020 [cited 2022 Dec 4];14:9-12. Available from:

   Introduction Top

In the past few decades, evidence-based medicine has emerged as a leading tool in explaining the relation between the blood group systems and systemic disorders based on immunological, histological, biochemical, and clinical findings.[1] Several studies have proposed the Lewis blood groups as the genetic marker for epidemiological screening in ischemic heart disease.[2],[3],[4] The role of Lewis blood group oligosaccharides in leukocyte-endothelium adhesion has been often thought to be the pivot in the pathogenesis of the cardiac disease. Exocrine epithelial cells secrete these fucosylated oligosaccharide antigens into plasma. These antigens are present in plasma as the high- and low-density lipoproteins (LDLs) and adsorbed on to red blood cell (RBC) membrane as glycolipids.[5] The distribution and expression of Lea and Leb phenotypes differ based on ethnicity, gender, and demography.[6],[7] The gene regulating their synthesis is in close association with LDL receptor gene, insulin receptor gene, and glycogen synthetase gene and may have bearing in the linkage disequilibrium on the 19th chromosome. There are reports showing a strong association between the absence of Lewis antigens and the coronary artery disease (CAD).[2],[3],[4],[8] On the other hand, some of the studies reported no such association in this regard.[9],[10] The present study was aimed to assess the association of Lewis phenotype as an independent risk factor for CAD and its utility as a standard screening test to prevent such occurrences in high-risk individuals.

   Materials and Methods Top

In this cross-sectional observational study, consecutive patients suspected for CAD, based on coronary angiography and catheterization, were enrolled in the study. The study was conducted after obtaining prior informed consent from individual patients and approval from the Institute's Ethics Committee. Those with angiographically proven CAD (defined as ≥50% luminal stenosis of coronary artery)[11] were included as “Test group,” and those with normal angiography were included as a control group. Individuals with <25 years of age and pregnant females were excluded from the study. Three hundred healthy voluntary blood donors were included as control group to ascertain the baseline frequency of Lewis phenotypes in the population [Figure 1]. Details about conventional CAD risk factors were recorded, which include smoking, diabetes mellitus, and hypertension, body mass index (BMI), waist–hip ratio, fasting blood sugar, lipid profile, and phenotyping for Lewis blood group systems.
Figure 1: Study design

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Red cell Lewis phenotyping was done using microcolumn gel agglutination technology[12] using ID-Card “DiaClon Anti-Lea” and “DiaClon Anti-Leb” (Biorad, California, USA). Modular P automated clinical chemistry analyzer (Roche, USA) was used to assess the biochemical profile of the individuals.

In a total of 232 consecutive patients subjected to coronary angiography, 161 patients had ≥50% luminal stenosis in a major epicardial artery (Test Group), and 71 had normal coronaries (Control Group). Of the total 232 enrolled patients, 161 were male (124 in the test group and 37 in control Group 1), and 71 were female (37 in the test group and 34 in control group). The study population was analyzed as two groups based on the results of Lewis antigen testing as Lewis-negative (Lewis [a−b−]) and Lewis-positive phenotype (Lewis [a+b−], Lewis [a−b+] and Lewis [a+b+]).

Statistical analysis

Chi-square test was applied to Lewis phenotype data, and logistic regression analysis was used to predict the Lewis phenotype as an independent predictor of CAD. ANOVA was applied for quantitative data comparison.

   Results Top

The frequency of established CAD risk factors was compared in the study population among patients with Lewis-negative and Lewis-positive phenotype separately in males and females to look for any association. Parameters such as fasting blood sugar, mean cholesterol, LDL, high-density lipoprotein (HDL), and triglycerides levels are comparable between Lewis-negative and Lewis-positive phenotype and P > 0.05 for both males and females. Physical parameters such as mean BMI and mean waist–hip ratio were also comparable in two groups, as summarized in [Table 1]. Hence, no association was found between established CAD risk factors and Lewis phenotypes.
Table 1: Comparison of Lewis blood group phenotypes as the risk factor for coronary artery disease among different genders

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There are some known risk factors for CAD as established in the literature.[13],[14],[15],[16] These risk factors (hypertension, smoking, diabetes, BMI, waist–hip ratio, and HDL levels) showed significant association with angiographically proven CAD.

The association of Lewis phenotype and coronary artery disease

When males and females were considered together, there was an increased frequency of lack of expression of Lewis antigen in the angiography-positive group (26.7%) when compared with angiography normal control group (16.9%), but this was not statistically significant (P = 0.19 %) [Table 2].
Table 2: Distribution of Lewis phenotypes in the study and control groups

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After applying multivariate analysis for removing the effects of other risk factors, the association of Lewis-negative phenotypes with CAD remained statistically insignificant with the P = 0.13.

When males and females were analyzed separately, Le (a−b−) females had a higher incidence of CAD (odds ratio [OR] 4.97, 95% confidence interval [CI] 1.2–21.2, P = 0.03) [Table 3], though it was not significant in males (P = 0.71).
Table 3: Lewis (a-b-) phenotypes and the risk of coronary artery disease in males and females on multivariate analysis

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   Discussion Top

Cardiovascular diseases are attributing to the significant burden of morbidity and mortality in developing countries, especially the urban areas is associated with various modifiable and nonmodifiable risk factors. The modifiable risk factors are such as diabetes, smoking, hypertension, obesity, dyslipidemia, and nonmodifiable risk factors are such as age, sex, race, and family history.[13],[14],[15],[16] We found a positive correlation between these risk factors with CAD.

Hein et al.[2] found individuals with a lack of expression of Lewis antigen had a higher BMI, a lower HDL level, a higher serum triglycerides level, and a higher risk of diabetes. Clausen et al.[4] also found Lewis-negative men had higher BMI, fasting insulin and glucose levels, and systolic blood pressure as compared to Lewis-positive phenotypes. However, in our study, no association was found between known risk factors such as BMI, waist–hip ratio, lipid profile, fasting blood sugar levels, and hypertension vis-a-vis Le (a-b-) phenotype, the observations were in line with the NHLBI Family Heart Study.[6]

The association of Lewis phenotypes with coronary artery disease

It has been observed that the Lewis-negative phenotype is associated with CAD. While some of the earlier studies[3],[4],[8] supported this association, other studies[9],[10] did not find any statistically significant correlation between the two. A study by Hein et al.[2],[17] showed a higher risk of CAD in males when there is a lack of Lewis antigen expression and showed a two-fold higher prevalence of nonfatal myocardial infarction among the males with Lewis-negative phenotype. In the NHLBI Family Heart Study,[6] the OR for CAD was 2.0 for the Lewis negative than the Lewis-positive phenotype, and the multivariate analysis, including all other risk factors, did not diminish the higher associated risk. Cakir et al.[9] evaluated the association of CAD, including the thickness of carotid arteries and presence of Lewis gene and found no association between lack of Lewis gene and carotid atherosclerosis (OR 1.23, 95% CI 0.70–2.16) compared to individuals with the presence of Lewis gene. These results are consistent with our study which did not find any significant correlation between Lewis-negative phenotypes and CAD. A study by Mansur et al.[10] found no association between the expression of Lewis antigen on RBC or saliva with CAD including acute myocardial infarction or abnormal lipid profile. The only study from India by Chaudhary and Shukla[3] found 2.5 times higher prevalence of Le (a−b−) phenotype in CAD patients posted for cardiac surgery as compared to healthy blood donors (29.1% vs. 9.6%, P < 0.01). In the present study, we found an increased frequency of Le (a−b−) phenotype in CAD patients compared to normal controls (26.7% vs. 16.9%, P = 0.194). However, when males and females were analyzed separately, Le (a−b−) females had a four-fold higher incidence of CAD (OR 4.97, 95% CI 1.2–21.2). If these results are extrapolated to population, Lewis-negative females can have 1.2–21 times higher incidence of CAD as compared to Lewis-positive females. Different results in our study from that by Chaudhary and Shukla[3] may presumably be due to the difference in the genetic makeup of the populations studied (Uttar Pradesh vs. Punjab), sample size, inclusion criteria and the prevalence of Lewis-negative phenotypes in the general population.

   Conclusion Top

The association between Lewis phenotypes and CAD was not significant in the overall population studied. However, it was statistically significant with regard to females, with hitherto unreported observation of higher prevalence of CAD among the females with Lewis-negative phenotype. This has the potential to define an independent risk factor as to devise the screening test to identify high-risk population subgroups. However, further studies on a larger number of patients are required to substantiate the observations as well as delineate possible hypotheses in support of these findings.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Garratty G. Blood groups and disease: A historical perspective. Transfus Med Rev 2000;14:291-301.  Back to cited text no. 1
Hein HO, Sørensen H, Suadicani P, Gyntelberg F. The Lewis blood group – A new genetic marker of ischaemic heart disease. J Intern Med 1992;232:481-7.  Back to cited text no. 2
Chaudhary R, Shukla JS. Association of Lewis blood group with ischaemic heart disease. Indian J Med Res 1999;109:103-4.  Back to cited text no. 3
Clausen JO, Hein HO, Suadicani P, Winther K, Gyntelberg F, Pedersen O. Lewis phenotypes and the insulin resistance syndrome in young healthy white men and women. Am J Hypertens 1995;8:1060-6.  Back to cited text no. 4
Henry S, Oriol R, Samuelsson B. Lewis histo-blood group system and associated secretory phenotypes. Vox Sang 1995;69:166-82.  Back to cited text no. 5
Thakral B, Saluja K, Sharma RR, Marwaha N. Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in north Indian blood donors. Transfus Apher Sci 2010;43:17-22.  Back to cited text no. 6
Nanu A, Thapliyal RM. Blood group gene frequency in a selected north Indian population. Indian J Med Res 1997;106:242-6.  Back to cited text no. 7
Ellison RC, Zhang Y, Myers RH, Swanson JL, Higgins M, Eckfeldt J. Lewis blood group phenotype as an independent risk factor for coronary heart disease (the NHLBI family heart study). Am J Cardiol 1999;83:345-8.  Back to cited text no. 8
Cakir B, Heiss G, Pankow JS, Salomaa V, Sharrett AR, Couper D, et al. Association of the Lewis genotype with cardiovascular risk factors and subclinical carotid atherosclerosis: The atherosclerosis risk in communities (ARIC) study. J Intern Med 2004;255:40-51.  Back to cited text no. 9
Mansur AP, Novaretti MC, Avakian SD, Ramires JA. Lack of association between Lewis phenotypes and ischemic heart disease. Sao Paulo Med J 2012;130:342-3.  Back to cited text no. 10
Lipinski M, Do D, Morise A, Froelicher V. What percent luminal stenosis should be used to define angiographic coronary artery disease for noninvasive test evaluation? Ann Noninvasive Electrocardiol 2002;7:98-105.  Back to cited text no. 11
Lapierre Y, Rigal D, Adam J, Josef D, Meyer F, Greber S, et al. The gel test: A new way to detect red cell antigen-antibody reactions. Transfusion 1990;30:109-13.  Back to cited text no. 12
James C. Risk factors for CADs: A study among patients with ischemic heart disease in Kerala. Heart India 2013;1:7-11.  Back to cited text no. 13
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Mohan V, Deepa R, Rani SS, Premalatha G. Prevalence of CAD and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). J Am Coll Cardiol 2001;38:682-7.  Back to cited text no. 14
Ali MK, Narayan KM, Tandon N. Diabetes and coronary heart disease: Current perspectives. Indian J Med Res 2010;132:584-97.  Back to cited text no. 15
[PUBMED]  [Full text]  
Meeran K, Bloom SR. Lewis phenotypes, insulin resistance, and risk of ischaemic heart disease. Br Heart J 1994;71:305-6.  Back to cited text no. 16
Hein HO, Suadicani P, Gyntelberg F. Lewis phenotypes, leisure time physical activity, and risk of ischaemic heart disease: An 11 year follow up in the Copenhagen male study. Heart 2001;85:159-64.  Back to cited text no. 17

Correspondence Address:
Dr. Hari Krishan Dhawan
Department of Transfusion Medicine, PGIMER, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.AJTS_15_19

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  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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