Investigation On Genetic Risks And Environmental Factors In Chinese Patients With Hyperlipidemia

Backgrounds:Dyslipidemia is a disorder of lipid metabolism in the blood and risk factors for atherosclerosis.Environmental factors,genetic factors,and their interaction can result in the increased lipids risks.Objectives:The aim of the present study(1)was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population;(2)was to present the cross-sectional associations of plasma total homocysteine(tHcy)concentrations and methylenetetrahydrofolate reductase(MTHFR)C677T genotype with dyslipidemia;(3)was to explore the effects of gender and CYP7A1-278A>C and SCARBI C1050T polymorphisms on the lipid level in Chinese essential hyperlipidemia.Methods:A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial.Plasma lipid levels and total leukocyte,neutrophil,and lymphocyte counts were determined according to standard methods.231 patients with mild-to-moderate essential hypertension were enrolled from the Huoqiu and Yuexi communities in Anhui Province,China.Plasma tHcy levels were measured by high-performance liquid chromatography.Genotyping was performed by TaqMan allelic discrimination technique;and 504 unrelated hyperlipidemic patients were included in this study.Genotyping of the SCARB1 C1050T and CYP7Al-278A/C were determined by PCR-RFLP.Results:(1)Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol(TC),LDL cholesterol(LDL-C),and triglyceride(TG)levels(all P<0.001 for trend),while inversely associated with HDL cholesterol(HDL-C)levels(P<0.05 for trend).In subsequent analyses where serum lipids were dichotomized(dyslipidemia/nonrmolipidemia),we found that patients in the highest quartile of total leukocyte count had 1.64 times the risk of high TG[95%confidence interval(CI):1.46,1.85],1.34 times the risk of high TC(95%Cl:1.20,1.50),and 1.24 times the risk of high LDL-C(95%CI:1.12,1.39)compared with their counterparts in the lowest quartile of total leukocyte count.Similar patterns were also observed with neutrophils and lymphocytes.(2)Compared with MTHFR 677 CC+CT genotype carriers,TT genotype carriers had higher odds of hypercholesterolemia(adjusted odds ratio[OR][95%(CI)]:2.7[1.4-5.2];P=0.004)and higher odds of abnormal LDL-C(adjusted OR[95%CI]:2.3[1.1-4.8];P=0.030).The individuals with the TT genotype had higher concentration of log(tHcy)than those with the 677 CC+CT genotype(adjusted(3[standard error]:0.2[0.03];P<0.001).Patients with tHcy>10 mmol/L had significantly higher odds of hypercholesterolemia(adjusted OR[95%CI]:2.4[1.2-4.7];P=0.010).Furthermore,patients with both the TT genotype and the tHcy≥10 mmol/L had the highest odds of hypercholesterolemia(adjusted OR[95%CI]:4.1[1.8-9.4];P=0.001)and low-density lipoprotein cholesterol(adjusted OR[95%CI]:2.4[1.0-6.0];P-0.064).(3)The CYP7A1-278 A>C variant was associated in male with lower total cholesterol and triglyceride concentrations compared with male homozygous for the common allele.However,serum lipid levels were not associated with SCARBI C1050T and CYP7A1-278A>C genotypes in women.Conclusions:In summary,these findings indicate that:(1)elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia.(2)both tHcy and the MTHFR C677T gene polymorphism may be important determinants of the incidence of dyslipidemia in Chinese patients with essential hypertension.(3)the SNP(C1050T)in SCARB1 gene and rs3808607 in CYP7A1 gene are independently associated with lipid parameters in a sex-dependent manner.