Potential unfavorable impacts of BDNF Val66Met polymorphisms on metabolic risks in average population in a longevous area.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi. METHODS: BDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60-77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60-75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined. RESULTS: As a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype. CONCLUSIONS: These data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring.

PPARD +294C overrepresentation in general and long-lived population in China Bama longevity area and unique relationships between PPARD +294T/C polymorphism and serum lipid profiles.

BACKGROUND: The +294T/C polymorphism in the peroxisome proliferator-activated receptor delta (PPARD) gene is associated with hyperlipidemia in several younger populations, but results are still inconsistence across ethnic groups and its possible impact on the lipid profiles of long-lived individuals remains unexploited. Here, we aimed to evaluate the possible correlation between PPARD +294T/C and serum lipid levels in a long-lived population in Bama, a region known for longevity situated in Guangxi, China. METHODS: Genotyping of PPARD +294T/C polymorphism was conducted in 505 long-lived inhabitants (aged 90 and above, long-lived group, LG) and 468 healthy controls (aged 60-75, non-long-lived group, non-LG) recruited from Bama area. RESULTS: No difference in allelic and genotypic frequencies was found between the two groups (P>0.05). However, C-allele and C-genotype (TC and CC) were significantly more frequent in the females of non-LG than were LG after sex stratification. CC carriers exhibited higher LDL-C level in LG (P<0.05) but lower TC, TG and LDL-C in non-LG (P<0.05 for each) than TT carriers; C allele carriers (TC/CC) in LG exhibited higher TC, TG, and LDL-C levels as compared with the same genotype and the same lipid parameter in non-LG (P<0.05 for each). LDL-C in LG was correlated with genotypes while TC, TG, and LDL-C in non-LG were correlated with genotypes (P<0.05-0.001). CONCLUSION: Our results suggest that there were different impact patterns of PPARD +294T/C polymorphism on lipid profiles between long-lived cohort and average population in Bama area and this may be one of the genetic bases of its longevity.

COMT Val158Met polymorphism is associated with blood pressure and lipid levels in general families of Bama longevous area in China.

To see the possible relationship between COMT Val158Met polymorphism and blood pressure (BP) and serum lipid levels and its putative role in human longevity, we genotyped COMT Val158Met (rs4680) by PCR-RFLP for members from Bama long-lived families (BLF, n = 1538), Bama non-long-lived families (BNLF, n = 600), Pingguo (a county outside Bama region) long-lived families (PLF, n = 538) and Pingguo non-long-lived families (PNLF, n = 403) after anthropometric measures were collected and serum lipid levels were detected. The distribution of genotypes and alleles among four family groups was significantly different (all P < 0.01), with GA/AA genotype and minor allele A presenting more frequently in Bama population than Pingguo Population (P < 0.01). The systolic blood pressure (SBP), pulse pressure (PP), total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) levels of GG genotype carriers were dramatically higher than non-GG carriers in BNLF (P < 0.05); the SBP and PP levels of GG carriers were lower (P < 0.05) while TC, LDL-C level were higher (P < 0.01) than that of non-GG carriers in PLF; no difference in blood pressure and lipids were observed between genotypes in BLF and PNLF (P > 0.05). Correlation analyses revealed that COMT Val158Met was mainly correlated negatively with SBP, diastolic blood pressure (DBP) and LDL-C in BNLF and negatively with TC level in BLF, BNLF and PLF. These data suggest that COMT Val158Met polymorphism may have more impact on the modulation of BP and lipid profiles in the average families than in the long-lived families in Bama region. The association between this SNP and other phenotypes (e.g. cognition) and its roles in the longevity in Bama area thus warrant further investigation.

Association between APOC1 polymorphism and Alzheimer's disease: a case-control study and meta-analysis.

BACKGROUND: Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer's disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. METHODS: To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. RESULTS: Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ(2) = 119.46, OR = 2.79, 95% CI = 2.31-3.36, P<0.01). CONCLUSIONS: The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.

Trans-ethnical shift of the risk genotype in the CETP I405V with longevity: a Chinese case-control study and meta-analysis.

BACKGROUND: The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity. METHODS: We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification. RESULTS: Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive =0.008; P dominant =0.008, OR(dominant)=0.673; P recessive =0.017, OR(recessive)=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans. CONCLUSION: Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.

[Association between SIRT1 gene polymorphisms and longevity of populations from Yongfu region of Guangxi].

OBJECTIVE: To assess the association between SIRT1 gene polymorphisms and the longevity phenomena in Yongfu region of Guangxi. In this case-control study, 500 individuals from Yongfu region of Guangxi were recruited. The subjects were divided into a longevity group (n=223, average age=93.17 U+00B1 3.08 yr) and a healthy control group (n=277, average age=46.92 U+00B1 17.12 yr). Polymerase chain reaction-high resolution melting curve (PCR-HRM) and DNA sequencing were used to determine the allelic and genotypic frequencies of rs3758391, rs3740051, rs2273773, rs4746720 and rs10997870 polymorphisms of SIRT1 gene in the two groups. The association between above polymorphisms and longevity was assessed. RESULTS: In the longevity group, CT genotype of the rs4746720 locus was significantly more common than CC and TT genotypes (P=0.000, OR=2.098, 95%CI:1.412-4.117). However, no significant difference was found in the allelic and genotypic frequencies of rs3758391, rs3740051 and rs2273773 between the two groups. CONCLUSION: There is an association between rs4746720 of SIRT1 gene and longevity in Yongfu region of Guangxi.

[Study on the longevity related mitochondrial genome variation in Bama elderly population in Guangxi province].

OBJECTIVE: To investigate the human mitochondrial DNA (mtDNA) variations associated with longevity in Bama elderly population from Guangxi. METHODS: Mitochondrial genome of 20 individuals over 96 years of age was sequenced, and seven target single nucleotide polymorphism (SNPs) were observed by comparing with the standard rCRS sequence, and two were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a larger population including 208 individuals of 90-113 years old, and 586 unrelated control individuals from Guangxi. RESULTS: The 4824G frequency of the mtDNA4824A/G locus increased with age both in the long-lived elderly and in controls. And it was significantly higher in controls than that in long-lived population (P<0.05). CONCLUSION: The mtDNA4824 A/G is not only an age-related locus, its mutation is also negatively correlated with longevity.

[The components of metabolic syndrome that influencing the prevalence of cardiovascular disease in a follow-up study].

OBJECTIVE: To investigate metabolic syndrome components that influencing the prevalence of cardiovascular disease (CVD). METHODS: Five hundred persons were selected from a unit in Nanning city, Guangxi, based on the cross-sectional study on a distribution of population with metabolic syndrome in 2004 and followed them up for 3.5 more years. Physical examination would include detection on blood pressure, glucose, serum cholesterol and body index etc. When someone suffered from cardiovascular disease would be viewed as an 'end-point event'. Criteria of diagnosis were under the basis of CVD from the WHO-MONICA. RESULTS: (1) The mean value of physical and biochemical index as BMI, waist circumstance, systolic pressure, diastolic pressure. Fast serum glucose, triglyceride in the population with more MS components were higher than the ones with less components. (2) The prevalence rates of CVD in the four groups were 2.97%, 4.19%, 7.97%, 11.88% respectively with significant differences between the groups (P = 0.0008). (3) Data from the logistic analysis manifested that when compared to the 0 group, the risk rate of CVD for groups having 1, 2, 3 components were 1.41, 2.68, 4.00 respectively. After adjusted age and sex, time of occurrences, results from the Cox model showed that the risk rate of CVD for groups with 1, 2, 3 components were 1.29, 2.47, 3.67 (RR 95%CI: 1.02 - 13.14) respectively. (4) Kaplan-Meier analysis showed that the cum hazard of CVD in the 3rd group was higher than in the 0, 1 group, and at the end of follow-up, the cum hazard of CVD was 12.7% in the 3rd group among population with metabolic syndrome. CONCLUSION: When increasing the number of components of metabolic syndrome, the higher risk ratio for population to suffer from CVD was seen. With the natural process of disease, the more components of metabolic syndrome in population, the higher cum hazard would influence the occurrence of CVD in the future.