Association Of Smoking, Drinking And Adiponectin Gene Polymorphisms With Alzheimer’s Disease

BackgroundAlzheimer’s disease (AD) is one of the most serious diseases in the world, and it isalso one of the main causes of death among the elderly. At present, the Chinese agingpopulation has been growing rapidly. In the next20-30years, it will reach the peak ofaging population in China. Accordingly, the prevalence of AD is a clear upward tendency.Therefore, there is an important task for medical community to prevent and manage theAD.The main causes of AD are association with lifestyle, related diseases and geneticfactors. Smoking and drinking is not only one kind of lifestyle, but also an importantvascular risk factor. Smoking and alcohol consumption was obviously higher in China thanthat in western countries, especially in male Chinese. There are some commonalities ofgenetic factors between Chinese populations and western populations, of course, as well assome differences. Therefore, it is important to discuss the relationship between AD andsusceptibility genes for AD prevention and management in China.Section One: Assotiation between smoking and drinking and ADBackgroundPrevious studies relating smoking and alcohol drinking with the incidence of dementiahave been inconsistent. We assessed whether smoking and alcohol drinking was associatedwith the risk of dementia, including AD and vascular dementia (VaD).MethodsFrom2004to2011, a total of2959elderly men from three districts in Chongqing citywere prospectively analysed the incidence of dementia, according to their smoking andalcohol drinking status. Cox proportional hazards models were established to evaluate theassociation between smoking, alcohol drinking and the risk of dementia. Results1. During follow-up,357cases of dementia were detected, of which172(48.2%) wasAD,156(43.7%) were VaD and29(8.1%) were other dementias. For the men whocompleted the follow-up, the average age was67.4±4.7years. Compared with the men whodid not develop dementia, those who did were significantly older, hypertension, diabetesmellitus, ischemic heart disease and stroke were more frequent in men with dementia, ADand VaD (p<0.01). Hypercholesterolemia was more prevalent in men with dementia, ADand VaD (p<0.05). ApoEε4was significantly more in men with dementia and AD (p<0.01),and VaD (p<0.05).2. The incidences of AD and VaD were higher respectively in current smoking thannever smoking, daily drinking than never drinking over7years of follow-up. Afteradjusting for age and other potential confounders, current smoking was associated withincreased risk of AD (HR=2.14,95%CI1.20-4.46) and VaD (HR=3.28,95%CI1.14-4.52), meanwhile, daily drinking was related to increased risk of AD (HR=2.25,95%CI1.43-3.97) and VaD (HR=3.42,95%CI1.18-4.51). In addition, co-smoking anddrinking were related to a significantly higher risk of AD (HR=3.03,95%CI1.65-4.19)and VaD (HR=3.96,95%CI1.64-4.71) than non-smoking and drinking. Moreover,co-smoking and drinking had higher risk of AD and VaD compared with current smokingand daily drinking.ConclusionsCurrent smoking and daily drinking were found to be significantly associated withdementia in elderly men.Section Two: Assotiation between AD and adiponectin gene polymorphismsBackgroundAdiponectin manifests anti-atherosclerosis and anti-inflammatory effects. Singlenucleotide polymorphisms (SNPs) in adiponectin gene have been related to hypertension,diabetes, stroke and serum of HDL-C levels. However, the association of SNPs inadiponectin gene with AD has never been studied before. Therefore, the aim of this study was to investigate the association between adiponectin gene SNPs and AD in middle agedand elderly subjects.MethodsConsecutive male inpatients aged60years and over of our department wereprospectively enrolled in this study. All participants underwent neuropsychological tests toassess the presence of AD. For statistical analyses, associations of AD with SNPs wereexamined by multivariate logistic regression analyses.Results1. From January2010to January2011, a total of906consecutive male subjects wereenrolled in the study. The mean age was67.1±8.4. Among the participants,425were casesand481were controls. The cases were older (P <0.05), and showed significantly higherproportion of hypertension, diabetes mellitus, prior stroke, and CAD (P <0.05), and higherlevels of systolic/diastolic BP and FBG (P <0.05) whereas lower levels of TC, HDL-C andApoA-I (P <0.05).2. More than97%samples were genotyped successfully for each SNP. Every groupconformed to the Hardy-Weinberg equilibrium (P>0.05).3. As for rs7649121, the AA, AT and TT genotype frequency were50.1%,42.5%and7.4%in AD case groups respectively, whereas61.0%,35.6%and3.4%in the control group.The distribution of genotypes was different between the two groups significantly (χ2=13.87, P=0.001). The A and T allele frequency were71.3%and28.7%in AD caseswhereas78.8%and21.2%in controls, showing significant difference (χ2=13.02, P <0.001). No differences in genotype or allele frequency were observed in rs1063539,rs2241767, rs1501299, rs16861194, rs12495941, rs182052and rs266729between ADcases and controls.4. After adjustment for age, prior stroke, CAD, hypertension, diabetes and HDL-Clevels, AT (OR=1.61,95%CI1.01-2.54) and TT(OR=3.46,95%CI1.22-10.07) wereassociated with higher risk of AD independently. In dominant model, AT/TT genotype was1.75times more likely to have AD than AA genotype.Conclusions1. Among the elderly male subjects, the present study firstly found that rs7649121inadiponectin gene might be associated with AD, and T allele was probably a susceptible allele of AD.2. We failed to find any association between AD and other SNPs in adiponectin geneincluding rs1063539, rs2241767, rs1501299, rs16861194, rs12495941, rs182052andrs266729.