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Correlational Study on Leptin Receptor Gene Pro1019Pro and Leptin Gene nt+19A→G Polymorphisms and Serum Leptin with Obstructive Sleep Apnea Hypoppea Syndrome

Author: GaoChunYan
Tutor: LiuYunQiu；LiHongFen
School: Hebei Union University
Course: Internal Medicine
Keywords: Leptin OSAHS gene polymorphism obesity
CLC: R766
Type: Master's thesis
Year: 2011
Downloads: 51
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Abstract

Objectives:1.To compare the serum leptin level of OSAHS patients and healthy people.2.To explorate the effect of the exon 20 of the leptin receptor gene Pro1019Pro polymorphism and the A19G Polymorphism in the 5’ Untranslated Region of the leptin gene on the affectability of Obstructive sleep apnea hypoppea syndrome (OSAHS).3.To explore the relations between risk factors with susceptibility of OSAHS.Methods:Case group involves 186 OSAHS male patients who visited Respiratory Department of KaiLuan hospital in Tang shan City during February 2010 to December 2010. (Table 2 shows OSAHS diagnostic criteria ).The 186 normal control people was recruited in medical examine centre at the same time.Using SRM-9601 polysomngraphy to monitor sleep conditions of all subjects for at least 7 hours at night. Selected patients have no complications, and except for exclusion criteria.According to body mass index (BMI),control group and case group as well were divided into 2 subgroups ,normal weight group and obese group (As a BMI>25 as the breaking point, the criteria of obesity in detail see Table 1). Physical examination and a unified questionnaire were performed and 8ml fasting blood samples were kept for the test of serum leptin’s level,total cholesterol triglycerides and the gene frequency of the two sites (Pro1019Pro nt+19A→G). The basic information such as name,age,height,weight,neck circumference,waist,abdomen circumference,buttocks circumference,blood pressure,marital status,occupation,level of education,past medical history,tobacco use,alcohol use,medication history and family history were collected from questionnaire. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of leptin in blood serum. Enzymatic oxidation was used to measure the level of triglycerides and total cholesterol in blood serum.To detect the genotypes of Leptin receptor gene Pro1019Pro and leptin gene nt+19A→G by using Polymerize chain reaction-Restriction fragment length polymorphism (PCR-RLFP) , To calculate the allele frequencies then.Multivariate logistic regression was used to explore the relativity of the risk factors and susceptibility of OSAHS. The data was analyzed by SPSS13.0 statistics package. A P value<0.05 was considered significant.Results:The serum leptin’s level in OSAHS group is significance higher than that in control group (15.77±4.88ng/ml vs 9.79±3.29ng/ml P<0.001). In specific, the level of leptin in OSAHS subgroups is higher than that in control subgroups respectively, in obesity group,18.40±3.27ng/ml and 12.64±1.96ng/ml (P<0.001), in normal weight group, 13.24±4.84ng/ml and 7.06±1.52ng/ml (P<0.001). To compare in the group(OSAHS group and control group as well) , the level of Leptin in the obesity subgroups is significantly higher than that in normal weight group (P<0.001).Between OSAHS and control group, the level of total serum cholesterol is similar in obesity subgroup (5.47±0.98mmol/L vs 5.29±0.74mmol/L P>0.05) and similar in normal weight subgroup(5.07±1.49mmol/L vs. 4.86±0.95mmol/L P>0.05). Not only in OSAHS group but also in control group, the level of total cholesterol have significance difference in obesity group and normal weight group(P<0.05)。The level of triglycerides in blood serum was2.56±1.31mmol/L in OSAHS combined obese group, the concentration was 2.02±1.25mmol/L in obese control group, significance difference was found (P<0.05). In normal weight group, the concentration of triglycerides were 2.02±0.79mmol/L and 1.68±1.19mmol/L in OSAHS and control group, significance difference was found (P<0.05). Not only in OSAHS group but also in control group, the level of triglycerides have significance difference in obesity group and normal weight group(P<0.05).The level of Low density lipoprotein cholestero(lLDL)in blood serum was2.42±0.84mmol/L in OSAHS combined obese group, the concentration was 2.10±0.65mmol/L in obese control group, significance difference was found (P<0.05). In normal weight group, the concentration of LDL were 2.13±0.75mmol/L and 1.85±0.60mmol/L in OSAHS and control group, significance difference was found (P<0.05). Both the OSAHS group or control group, the obese group compared with the normal weight group, the difference was statistically significant (P <0.05)。The frequency of genotype of leptin receptor Pro1019Pro were: GG-18(9.7%), GA-30(16.1%) and AA-138(74.2%) in OSAHS group and GG-22(11.8%), GA-38(20.4%) and AA-126(67.8%) in control group. The distribution of genotypes in the 2 groups was not significant difference (P= 0.596). The frequency of genotype of leptin nt+19A→G were: AA-34(18.3%), GA- 69(37.1%) and GG-83(44.6%) in OSAHS group and AA-29(15.6%), GA-88(47.3%) and GG-69(37.1%) in control group. The distribution of genotypes in the 2 groups was not significant difference (P= 0.136).In total, the frequency of allele G in leptin receptor gene 3057 site were 17.7% and 22.6% in OSAHS group and control group, the frequency of allele A of 3057 site were 82.3% and 77.4% in OSAHS group and control group, no significant difference was found (P=0.100).The frequency of allele G of nt+19A→G site in leptin gene were 63.2% and 60.8% in OSAHS group and control group, the frequency of allele A of nt+19A→G site in leptin gene were 36.8% and 39.2% in OSAHS group and control group, no significance difference was found (P=0.497). Not only in total but also in subgroup of obesity and normal weight, the differences of allele frequency in two sites were not found (P>0.05).The rate of smoking were 57.5% and 38.7% in OSAHS and control group, the difference was significant (P=0.000). The rate of with family history of snoring were 36% and 22.6% in OSAHS and control group, the difference was significant (P=0.004).The results of multivariate Logistic regression show that age,increased neck circumference,smoking,with family history of snoring,upper airway abnormalities could increase the risk of OSAHS. The risk of OSAHS in person with family history was 2.328 times than person not with family history. The 95% confidence interval (CI) was 1.205 to 4.497. Smoking can increase the risk of OSAHS 1.858 times and the 95%CI was 1.028to 3.360. The risk of OSAHS in person with upper airway structural abnormalities was 2.135 times than person not with upper airway structural abnormalities, the 95% confidence interval (CI) was 1.081 to 4.219. Age was a risk factor for OSAHS, but its specific impact on OSAHS need further study.Conclusion:1. The consentration of leptin in serum of OSAHS suffer is marked higher than normal people.2. Leptin receptor gene Pro1019Pro polymorphisms and the A19G Polymorphism in the 5’ Untranslated Region of the Leptin gene do not affect serum leptin levels and lipid levels, The polymorphism have no relations with OSAHS.3. Age, increased neck circumference, smoking, family history of snoring and upper airway structural abnormalities were the risk factors of OSAHS. They could increase the risk of OSAHS.

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