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The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis

The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis
The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis
Background There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD). Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies.
Results The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval) of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association) was 1.03 (0.89, 1.21) and the per allele odds ratio was 0.98 (0.95, 1.01). In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls) the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20) and for the per allele effect was 1.10 (1.06, 1.13). There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15). Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia).
Conclusion There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.
meta-analysis, case-control studies, heart, sex, risk, population, male, health, diabetes, polymorphism, disease, coronary disease, genetic, glutamine, coronary heart disease, non-u.s.gov't
1471-2156
1-12
Lawlor, Debbie A.
799826df-f115-4fb7-83ea-53c246c220d4
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Hinks, Lesley J.
26543550-2e57-4947-9737-25c4c4ab1163
Briggs, Patricia J.
a6d4be22-a8e6-4951-bed9-9af5b287cfec
Kiessling, Matthew
30f977bd-1bbb-4f67-9d2a-142266643ec9
Timpson, Nick
91f6a11f-f375-43d7-87f9-ede6f090f161
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Ebrahim, Shah
0f2ade5c-4ef6-4ca7-9f9b-9b60ba192b13
Lawlor, Debbie A.
799826df-f115-4fb7-83ea-53c246c220d4
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Hinks, Lesley J.
26543550-2e57-4947-9737-25c4c4ab1163
Briggs, Patricia J.
a6d4be22-a8e6-4951-bed9-9af5b287cfec
Kiessling, Matthew
30f977bd-1bbb-4f67-9d2a-142266643ec9
Timpson, Nick
91f6a11f-f375-43d7-87f9-ede6f090f161
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Ebrahim, Shah
0f2ade5c-4ef6-4ca7-9f9b-9b60ba192b13

Lawlor, Debbie A., Day, Ian N.M., Gaunt, Tom R., Hinks, Lesley J., Briggs, Patricia J., Kiessling, Matthew, Timpson, Nick, Smith, George Davey and Ebrahim, Shah (2004) The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC Genetics, 5 (17), 1-12. (doi:10.1186/1471-2156-5-17).

Record type: Article

Abstract

Background There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD). Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies.
Results The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval) of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association) was 1.03 (0.89, 1.21) and the per allele odds ratio was 0.98 (0.95, 1.01). In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls) the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20) and for the per allele effect was 1.10 (1.06, 1.13). There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15). Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia).
Conclusion There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.

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More information

Published date: 23 June 2004
Keywords: meta-analysis, case-control studies, heart, sex, risk, population, male, health, diabetes, polymorphism, disease, coronary disease, genetic, glutamine, coronary heart disease, non-u.s.gov't

Identifiers

Local EPrints ID: 59969
URI: https://eprints.soton.ac.uk/id/eprint/59969
ISSN: 1471-2156
PURE UUID: ef60c469-8486-4cc0-9e6f-a5fc0d531b64

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Date deposited: 05 Sep 2008
Last modified: 13 Mar 2019 20:30

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