Correlation Between GHSR And GHRL Polymorphism And Blood Glucose And Lipid Levels In Long-Lived Population

BackgroundGhrelin (GHRL) is the natural ligand of growth hormone releasing hormone receptor (GHSR). When it binds to its receptor GHSR it plays important roles in physiological regulation and disease development in humans, including the promotion of appetite and digestion, the protection of the function of gastrointestinal tract, the regulation of blood lipi ds, the inhibition of inflammatory reaction, the suppression of tumoral cell proliferation and other functions. Very recently, GHRL/GHSR has been linked to metabolic risks such as BMI, blood pressure, lipid profiles and blood glucose, all of which may affect age-related disorders and lifespan.ObjectivesTo investigate the correlation between GHSR rs572169 and GHRL rs26802 polymorphisms and blood lipid and glucose levels, in an attempt to further reveal the putative roles it may play in the longevity of the region.Methods1830 individuals were enrolled from the longevity region along the Red River Basin in Guangxi including three groups:longevity group (n=496),723 offspring group (n=723) and control group (n=611). Height, weight, BMI, blood pressure, blood sugar and blood lipids were measured and inputted as baseline data. Improved multi-temperature ligase detection reaction (improved multiple ligase detection reaction, iMLDR) method was employed to genotype GHSR rs572169 and GHRL rs26802 loci. Association analyses were performed between the two SNPs and blood glucose and lipid levels afterwards.Results1. General information:Blood glucose of longevity group was lower than the other two groups, while systolic diastolic blood pressure was higher than the other two groups; longevity group exhibited lower TG level but higher HDL-C level as compared to the controls.2. GHSR genotype and allele frequencies:the freqencies of the major allele of GHSR rs572169 in longevity, offspring and control group were 65.4%,62.7% and 61.5% respectively; heterozygous genotype CT was the major genotype. The genotype and allele frequencies among the three groups showed no significant difference. Females in longevity group exhibited lower T allele genotype (CT/TT) frequency delete than the control group.3. GHSR gene polymorphisms on blood glucose and lipid levels:group T allele TC levels above non-T carriers. Stratified by gender, women and children overall group of women in TG levels, blood glucose levels of male control group, T allele were higher than T carriers.4. GHSR genotype and serum lipid levels:the lipid layers, group dyslipidemia subgroup, T allele of TC and HDL-C levels were significantly higher than the non-T carriers, other groups the genotype TT and TC/CC effects on dyslipidemia is not obvious.5. GHSR correlation between genotype and BMI:BMI stratified, overall BMI normal subgroup TG value and longevity of the group with normal BMI subgroups normal levels of blood glucose and TG subgroups TC values and LDL-C values, the control group BMI, T allele were higher than non-T carriers.6. GHSR correlation between genotype and pulse pressure:pulse pressure stratification, group pulse pressure increases subgroups, TC levels of T allele carriers than non-T, and T allele HDL-C levels of gene carriers is lower than T carriers.7. GHSR genotype correlation with blood glucose levels:Blood sugar stratification, overall hyperglycemia subgroup, T allele of HDL-C/LDL-C levels lower than T carriers; children and control of blood glucose blood sugar levels are normal subgroup of T allele increased; control group, hyperglycemia subgroup, T allele of LDL-C levels than non-T carriers.8. GHRL genotype and allele frequencies:alleles in longevity groups, children and control groups are T-based, frequency of 89.4%,90.5% and 89.4% respectively; the main TT homozygous genotype The genotype and allele frequencies among the three groups showed no significant difference.9. GHRL gene polymorphisms on blood glucose and lipid levels:children group of wild-type TT’s high HDL-C levels in the control group G allele LDL-C levels than non-G carriers. Gender stratification, group male longevity glucose levels in the control group of women in the TC levels and LDL-C levels were higher than G allele G carriers; child group of women in HDL-C level was higher than the wild-type TT TG/GG.10. GHRL genotype and serum lipid levels:the children group of wild-type gene TT dyslipidemia higher frequencies. Lipid layers, longevity group and children group normal lipid subgroup, G allele glucose levels were significantly higher than G carriers; HDL-C level children group dyslipidemia subgroup compared with wild-type TT TG/GG high.11.GHRL correlation between genotype and BMI:BMI stratified, the blood sugar level, blood sugar level BMI longevity Group G allele carriers normal subgroups and normal subgroups of children group than non-carriers G high. On lipid levels, overall BMI overweight LDL-C levels and longevity group BMI subgroup normal subgroup of children group of normal subgroups TG levels were compared with wild-type TT TG/GG high; group of overweight children subgroup of genotype TT HDL-C levels than TG/GG high; in the control group, the subgroup of overweight, G allele of TC, LDL-C levels than non-carriers G high.12.GHRL correlation between genotype and pulse pressure:pulse pressure difference in overall normal subgroup, TG levels lower than G allele G carriers. Longevity group increased pulse pressure and blood sugar levels subgroup control group increased pulse pressure subgroup LDL-C levels were higher than non-G G allele carriers.13. GHRL genotype correlation with blood glucose levels:Blood sugar stratification in subgroups of children of normal blood glucose levels of HDL-C compared with wild-type genotype TT TG/GG high; longevity blood glucose normal subgroup, the wild-type gene TT type high LDL-C levels; the control group with normal blood glucose subgroup, G allele of LDL-C levels than non-G carriers.Conclusions1. Long-lived individuals displayed significant blood pressure, blood glucose, BMI, triglyceride (TG) and high density lipoprotein (HDL-C) levels as compared to general population.2. GHSR rs572169 and GHRL rs26802 genotype and allele frequency showed no significant difference between longevity group and the control group, but GHSR rs572169T allele was significantly enriched in the control females.3. GHSR rs572169 and GHRL rs26802 mutant allele have a negative impact on the the lipids and glucose modulation in Hongshui River longevity region.