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Association Study On The APOC1 Rs4420638 Polymorphisms With Lipids In Longevity Of Guangxi Hongshuihe River Basin

Posted on:2016-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y WangFull Text:PDF
GTID:2284330461470572Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Background:Apolipoprotein is a part of lipoprotein in plasma. There are five kinds of apolipropotein, including apolipoprotein A, B, C, D and E. The functions of these apolipoproteins are to transport lipid and stabilize the structure of lipoprotein. Some of the apolipoproteins also can ativate enzyme which is association with lipoprotein metabolism and identify receptor. It is not fully clearly about the function of apolipoprotein C1 in lipoprotein metabolism.With the development of genetic technology, there have been some progresses about association study on APOC1 polymorphisms with lipoprotein metabolism.Objectives:The aims of the current study are to explore the APOC1 rs4420638 polymorphism in the long-living population residing Guangxi Hongshuihe River basin and explore its possible association with lipid level and human longevity in the region.Methods:Genotyping of the APOC1 rs4420638 polymorphism was conducted by improved multiplex ligation detection reaction (iMLDR). Physical examinations including blood pressure, body weight, height, body mass index were performed and serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels were measured for 496 Zhuang long-lived inhabitants (aged 90 and above, longevity group),723 offspring of longevity (age 60-75, offspring group) and 611 ethnicity and age-matched healthy controls (aged 60-75, control group) residing in Hongshuihe River Basin, northwest Guangxi Province.Results:1. General clinical characteristics and lipid levels:Blood pressure were significantly higher in longevity group than in offspring group and control group (P<0.001). TC, TG, HDL-C, HDL-C/LDL-C level were significantly lower in longevity group than offspring group (p<0.001). TC, TG, HDL-C and HDL-C/LDL-C levels were significantly lower in control group than offspring group (p<0.001). FPG level was significantly lower in longevity group than in offspring group and control group (P<0.005). FPG level were significantly lower in offspring than control (p<0.001).2. Genotypes:The dominant allele of APOC1 rs4420638 in longevity group, offspring group and control group are A (92.3%,90.6% and 90.9%, respectively). No significantly difference allelic and genotypic frequency on APOC1 rs4420638 locus was found among the three groups. There were also no significantly different stratified by gender.3. Allelic and genotypic frequency (when stratified by lipid level):No significantly different allelic and genotypic frequency on APOC1 rs4420638 locus was found among the three groups when stratified by lipid level. In women of longevity and control group, there was significantly different allelic and genotypic frequency on APOC1 rs4420638 locus between dyslipidemia subgroup and normal lipidemic subgroup (p=0.034 and p=0.032). And in men of longevity group there was significantly different frequency between dyslipidemia subgroup and normal lipidemic subgroup (p=0.047).4. Allelic and genotypic frequency (when stratified by BMI):No significantly different allelic and genotypic frequency on APOC1 rs4420638 locus was found among the three groups when stratified by BMI. Then stratified by gender found that in men of control group there was significantly different frequency between normal weight subgroup and overweight subgroup (p=0.032).5. Relationship between genotypes and lipid levels:The TC and LDL-C levels of G allele carriers was significantly higher than non-G allele carriers (p<0.05) in total and control group.6. Relationship between genotypes and lipid levels (when stratified by gender):The TC, LDL-C levels of G allele carriers was significantly higher than non-G allele carriers (p<0.05). The TC, LDL-C level of G allele carriers were significantly higher than non-G allele carriers (p<0.05) in women of longevity group. The TC level of G allele carriers were significantly higher than non-G allele carriers (p<0.05) in men of control group. The LDL-C level of G allele carriers were significantly higher than non-G allele carriers (p<0.05) in women of control group. There was no significantly difference about lipid levels between two genotypes when satisfied by gender in offspring group.7. Relationship between genotypes and two lipid levels:In normal lipidemic subgroup, the TC and LDL-C level of G allele carriers were significantly higher than non-G allele carriers (p=0.005 and p=0.003). In normal lipidemic subgroup of offspring group, the LDL-C level of G allele carriers was significantly than non-G allele carriers. In control group, the TC level of G allele carriers was significantly higher than non-G allele carrier both in dyslipidemia subgroup and normal lipidemic subgroup (p=0.037 and p=0.034).8. Relationship between lipid levels and BMI:In total, the TC, TG and LDL-C levels of overweight BMI subgroup were significantly higher than normal weight BMI subgroup. After stratified by gender, there was the same finding. In longevity group, there was no significantly difference between overweight BMI subgroup and normal weight BMI subgroup, even after stratified by gender. In offspring group, the TC, TG, and LDL-C levels of overweight BMI were significantly higher than normal weight BMI subgroup. After stratified by gender in offspring group, there was the same finding. In control group, the LDL-C levels of overweight BMI were significantly higher than normal BMI subgroup. There was the same finding in men of control group.9. Relationship between genotypes and two BMI subgroup:In normal weight subgroup of study population, the TC and LDL-C level of G allele carriers were significantly higher than non-G allele carriers (p=0.005 and p=0.003); In normal weight BMI of offspring group, the LDL-C level of G allele carriers was significantly higher than non-G allele carriers(p=0.035). In control group, the TC level of G allele carriers was significantly higher than non-G allele carriers both in normal weight BMI and overweight BMI subgroup. (p=0.037 and p=0.034).10. Linear regressive analysis:In total study population, TC and LDL-C levels were negatively associated with genotype. In control group, TC, LDL-C and HDL-C level was negatively associated with genotype. (1)In study population, TC level was positively associated with BMI, gender, diastolic blood pressure (DBP) and negatively associated with age; TG level was positively associated with FPQ BMI and DBP and negatively associated with gender and age. HDL-C level was positively associated with DBP and negatively associated with BMI, FPG and age; LDL-C level was positively associated with gender and BMI. (2) In longevity group, TC level was positively associated with DBP and gender; TG level was positively associated with FPG, BMI and gender; HDL-C level was positively associated with SBP and negatively associated with BMI; LDL-C level was positively associated with DBP. (3) In offspring group, TC level was positively associated with BMI, gender and FPG; TG level was positively associated with FPG and BMI and negatively associated with gender; HDL-C level was negatively associated with BMI and FPG; LDL-C level was positively associated with gender and BMI and negatively associated with DBP. (4) In the control group, TC level was positively associated with gender and negatively associated with FPG; HDL-C level was negatively associated with PP, FPG and gender; LDL-C level was positively associated with gender and BMI and negatively associated with FPG.Conclusions:1. There are significant diversities on the blood pressure and lipid profiles among three groups in Guangxi Hongshuihe river basin.2. Overall, there are no differences on the distribution of allelic and genotypic frequencies of APOC1 rs4420638.3. G allele carriers of APOC1 rs4420638 tend to increase lipid level in individuals from Guangxi Hongshui River region, but its effect on the longevity in this area needs further investigation.
Keywords/Search Tags:APOC1 rs4420638, gene polymorphism, lipoprotein, longevity
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