Effect of SORT1, APOB and APOE polymorphisms on LDL-C and coronary heart disease in Pakistani subjects and their comparison with Northwick Park Heart Study II.
BACKGROUND
Many SNPs have been identified in genes regulating LDL-C metabolism, but whether their influence is similar in subjects from different ethnicities is unclear. Effect of 4 such SNPs on LDL-C and coronary heart disease (CHD) was examined in Pakistani subjects and was compared with middle aged UK men from Northwick Park Heart Study II (NPHSII).


METHODS
One thousand nine hundred sixty-five (1770 non CHD, 195 CHD) UK and 623 (219 non CHD, 404 CHD) Pakistani subjects were enrolled in the study. The SNPs SORT1 rs646776, APOB rs1042031 and APOE rs429358, rs7412 were genotyped by TaqMan/KASPar technique and their gene score was calculated. LDL-C was calculated by Friedewald equation, results were analyzed using SPSS.


RESULTS
Allele frequencies were significantly different (p= <0.05) between UK and Pakistani subjects. However, the SNPs were associated with LDL-C in both groups. In UK non CHD, UK CHD, Pakistani non CHD and Pakistani CHD respectively, for rs646776, per risk allele increase in LDL-C(mmol/l) was 0.18(0.04), 0.06(0.11), 0.15(0.04) and 0.27(0.06) respectively. For rs1042031, per risk allele increase in LDL-C in four groups was 0.11(0.04), 0.04(0.14), 0.15(0.06) and 0.25(0.09) respectively. For APOE genotypes, compared to Ɛ3, each Ɛ2 decreased LDL-C by 0.11(0.06), 0.07(0.15), 0.20(0.08) and 0.38(0.09), while each Ɛ4 increased LDL-C by 0.43(0.06), 0.39(0.21), 0.19(0.11) and 0.39(0.14) respectively. Overall gene score explained a considerable proportion of sample variance in four groups (3.8%, 1.26% 13.7% and 12.3%). Gene score in both non-CHD groups was significantly lower than CHD subjects.


CONCLUSIONS
The SNPs show a dose response association with LDL-C levels and risk of CHD in both populations.
Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan. saleemullahshahid@hotmail.com.
Saleem Ullah
SU
Shahid
Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Shabana
S
ᅟ
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, WC1E6JF, UK.
Jackie A
JA
Cooper
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, WC1E6JF, UK.
Katherine E
KE
Beaney
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, WC1E6JF, UK.
Kawah
K
Li
Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Abdul
A
Rehman
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, WC1E6JF, UK.
Stephen Eric
SE
Humphries
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000368:Aged; D053299:Apolipoprotein B-100 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D053299:Apolipoprotein B-100; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D000099183:Sortilin; C569471:APOB protein, human; C000612345:ApoE protein, human
APOB; APOE; Gene score; LDL-C; SORT1