1. Jae Woong Sull, Sun Ha Jee Eulji University, Yonsei University
Association of CDH13 Polymorphisms with Serum Adiponectin Levels in a Korean Population
Jae Woong Sull, Sun Ha Jee
Eulji University, Yonsei University

2. Background
Adiponectin is associated with obesity and insulin resistance.
Several genome-wide association studies of adiponectin levels have identified candidate genes, including the CDH13 gene.
Rule of thumb - Gender Inequality
Women become intoxicated more quickly than men, even when body weights are the same. There are three likely explanations for this fact.
First, soon after consumption, alcohol rapidly spreads throughout the water in a drinker’s body, and men’s bodies have a greater percentage of water by volume. If a woman drinks the same amount as a man, the effect is similar to pouring the same amount of alcohol into a smaller pail of water.
Women also have lower levels of activity in the alcohol-metabolizing enzyme, alcohol dehydrogenase, in the stomach. This means that more alcohol is metabolized in the stomachs of men before being absorbed into the bloodstream than in the stomachs of women. The end result is that more alcohol passes directly into the bloodstream of women.
Finally, as a woman’s hormone levels vary during the course of her menstrual cycle, her blood alcohol concentration can vary dramatically with the same amount of alcohol intake.

3. We genotyped for 990 subjects with the Affymetrix Genome-wide Human SNP array 5.0. Serum adiponectin levels were measured. For statistical analysis, we used multivariate linear regression model using PLINK. In the model, we adjusted age, sex, and smoking status and we used additive model.

4. Significance of SNPs in CDH13 for all 3 cohorts
The upper part of the plot shows the -log10 P value. Black, red, and white solid spots are  respectively of the discovery study, of 1st replication and of 2nd replication. The lower part of the plot shows the recombination rate across the region (blue) and the cumulative recombination rate measured away from the most highly associated SNP of rs (yellow). Positions of highly significant SNPs were upstream of CDH13.

5. Study Objective
to examine the association of serum adiponectin levels (or hypoadiponectinemia) with SNPs in CDH13 gene considering fasting blood glucose levels and smoking status.

6. Study Population
A total of 4,294 subjects were recruited from a Hospital, Korea.
2289 subjects were excluded due to missing BMI and adiponectin level data. Thus, the final population included 2,005 subjects.
The institutional Review Board at Yonsei University

7. Definition of Hypoadiponectinemia
Hypoadiponectinemia was defined as the lowest quartile of adiponectin (<4.27 for all subjects, <3.85 for Men, <6.01 for Women).

8. Genotyping
The CDH13 gene SNPs were genotyped via the TaqMan reaction. Duplicate genotyping for 1–2.5% of all samples was carried out as a QC measure.

9. Statistical Analysis
Most statistical analyses were performed using PLINK and SAS ver. 9.2 (SAS Institute, Cary, NC, USA).
The multivariate linear regression models used in the study incorporated covariates (age and sex).
Multiple logistic regression analysis was also performed.

10. Table 1. General characteristics of study population
Subjects
All
Men
Women N
2005
1412
593
Mean ± SD
Age, year
50.6±9.8
50.6±9.7
50.8±9.6
Waist circumference, cm
83.4±9.0
86.5±7.7
76.9±8.2
Body mass index, kg/m2
24.2±2.9
24.8±2.8
23.0±2.9
Fasting blood sugar, mg/Dl
96.3±22.0
98.4±23.8
91.2±15.8
Adiponectin, μg/ml
7.59±4.97
6.51±4.15
10.15±5.76
Systolic blood pressure, mmHg
121.7±14.3
123.3±13.9
117.9±14.4
Diastolic blood pressure, mmHg
77.8±10.9
79.3±10.8
74.0±10.2 %
Smoking status Ex
28.6
39.7
1.6
Current
27.3
37.3
3.0
Diabetes*
7.9
9.2
4.9
Family history of diabetes
15.9
15.2
17.5

11. Fasting blood sugar, mg/dL
Table 2. Association between the rs single nucleotide polymorphism in the CDH13 gene and adiponectin levels based on a linear regression model
Genotypes
Phenotypes GG
(N=1009) TG
(N=820) TT
(N=176)
Effect
(mg/dL)
P-value*
Mean±SD
Adiponectin, μg/ml
8.52±5.3
6.81±4.4
5.86±4.0
1.511
<0.0001
Fasting blood sugar, mg/dL
96.6±22.2
95.2±20.2
99.4±28.0
-0.367
0.6218
Body mass index, kg/m2
24.2±3.0
24.2±2.8
24.5±3.1
-0.065
0.5033
Estimated effect size (β) and p-value in the multiple linear regression model considered age and sex in the additive model.

12. Hypoadiponectinemia *
Table 3. Odds ratios of rs CDH13 genotypes for hypoadiponectinemiaa (n = 2,005)
Normal
Hypoadiponectinemia *
Subjects
Genotype
N (%)
OR (95% CIb)
P-value
All GG
836 (55.5)
173(34.7)
1.00 (reference)
TG/TT
670 (44.5)
326(65.3)
2.44( )
<0.0001
Men
594 (56.0)
117(33.3)
467 (44.0)
234(66.7)
2.56( )
Women
245 (55.1)
53(35.8)
200 (44.9)
95(64.2)
2.19( )
a Adjusted for age and sex b CI, confidence interval
* Hypoadiponectinemia was defined as the lowest quartile of adiponectin.

13. Hypoadiponectinemia*
Table 4. Odds ratios (OR) of polymorphic rs CDH13 genotypes for hypoadiponectinemiaa in the population (n = 2,005)
Normal
Hypoadiponectinemia*
Subjects
Genotype
N (%)
OR (95% CIb)
P-value
FBS<110 GG
741(54.6)
147(36.1)
1.00 (reference)
TG/TT
616(45.4)
260(63.9)
2.19( )
<0.0001
110≤FBS<126
49(67.1)
8(17.4)
24(32.9)
38(82.6)
10.96( )
FBS≥126
46(60.5)
18(39.1)
30(39.5)
28(60.9)
2.72( )
0.0120
Family history of Diabetes (No)
693(54.1)
142(34.9)
587(45.9)
265(65.1)
2.26( )
Family history of Diabetes (Yes)
143(63.3)
31(33.7)
83(36.7)
61(66.3)
3.80( )
a Adjusted for age and sex b CI, confidence interval
* Hypoadiponectinemia was defined as the lowest quartile of adiponectin.

14. Table 5. Odds ratios (OR) of polymorphic rs CDH13 genotypes for hypoadiponectinemiaa in Korean men (n = 1,412)
Normal
Hyponectinemia*
Subjects
Genotype
N (%)
OR (95% CIb)
P-value
Non smokers GG
144(58.3)
16(23.2)
1.00 (reference)
TG/TT
103(41.7)
53(76.8)
4.67( )
<0.0001
Ex smokers
224(54.0)
43(32.8)
191(46.0)
88(67.2)
2.44( )
Current smokers
211(57.2)
56(38.9)
158(42.8)
88(61.1)
2.17( )
0.0001
a Adjusted for age and sex b CI, confidence interval
* Hypoadiponectinemia was defined as the lowest quartile of adiponectin.

15. Summary / Discussion
In this study, SNPs in CDH13 gene were associated with hypoadiponectinemia, consistent with previous studies.
In the present study, we found that CDH13 SNP had a stronger association with hypoadiponectinemia in subjects with impaired fasting glucose levels than Normal subjects

16. Conclusions
The association of CDH13 gene SNP was stronger in nonsmokers than that in mokers.
In conclusion, this study clearly demonstrates that genetic variants in CDH13 gene influence serum adiponectin levels in Korean adults.

17. Thank you !